47 results on '"Dong, A-liang"'
Search Results
2. Metformin induces apoptosis in mesenchymal stromal cells and dampens their therapeutic efficacy in infarcted myocardium
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Xiao He, Meng-Wei Yao, Ming Zhu, Dong-Lan Liang, Wei Guo, Yi Yang, Rong-Seng Zhao, Ting-Ting Ren, Xiang Ao, Wei Wang, Chun-Yu Zeng, Hua-Ping Liang, Dong-po Jiang, Jian Yu, and Xiang Xu
- Subjects
Mesenchymal stromal cells ,Metformin ,Myocardial infarction ,Apoptosis ,Diabetes mellitus ,Medicine (General) ,R5-920 ,Biochemistry ,QD415-436 - Abstract
Abstract Background Cardiovascular complications, especially myocardial infarctions (MIs), are the leading mortality cause in diabetic patients. The transplantation of stem cells into damaged hearts has had considerable success as a treatment for MI, although whether antidiabetic drugs affect the therapeutic efficacy of stem cell transplantation is still unknown. This study aims to understand whether and how metformin, one of the first-line drugs used to treat type 2 diabetes mellitus (T2DM), induces mesenchymal stromal cell (MSC) apoptosis and dampens their cardioprotective effect after transplantation into infarcted hearts. Methods A mouse MI model was generated via permanent ligation of the left anterior descending (LAD) coronary artery. MSCs with or without metformin treatment were transplanted after MI in diabetic mice. Echocardiography was used to assess cardiac function and determine cardiac remodeling, and TTC staining was performed to evaluate infarction size. A mouse gavage model was performed to evaluate bone marrow MSCs for flow cytometry assay. Results Metformin dampened MSC therapeutic efficacy, which increased infarct size and restricted functional cardiac recovery. Specifically, metformin induced the activation of AMP-activated protein kinase (AMPK)-mediated apoptosis through the inhibition of S6K1-Bad-Bcl-xL cell survival signaling, resulting in the upregulated expression of apoptosis-associated proteins and increased MSC apoptosis. Accordingly, counteracting AMPK attenuated metformin-induced apoptosis in MSCs and partially restored their cardioprotective effects in diabetic mice with MI. Furthermore, a decrease in peripheral blood MSCs was found in patients with T2DM who had a metformin medication history. Conclusions Our results highlight an unexpected adverse effect of metformin-induced MSC apoptosis through AMPK-mediated mTOR suppression, which is attenuated by an AMPK inhibitor. Moreover, AMPK inhibition may be a novel strategy for enhancing the effectiveness of stem cell therapy after MI in diabetes.
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- 2018
- Full Text
- View/download PDF
3. New ingenane diterpenoids from Euphorbia kansui reverse multi-drug resistance
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You Chen, Dong-E Liang, Di Luo, Lie-Feng Ma, Ning-Yu Chen, Yue Zhang, and Zha-Jun Zhan
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Drug ,010405 organic chemistry ,Chemistry ,media_common.quotation_subject ,Adenocarcinoma cell ,Plant Science ,Drug resistance ,Adriamycin resistant ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Cancer research ,Euphorbia kansui ,MDR Modulators ,Agronomy and Crop Science ,Human breast ,Biotechnology ,media_common - Abstract
Ten ingenane-type diterpenoids, including two undescribed compounds named as kansuininols A–B (1–2), were isolated from the roots of Euphorbia kansui. Their structures were elucidated by detailed interpretation of their spectroscopic data, especially 2D-NMR and HR-ESI-MS. Chemoreversal assays of these isolates were carried on adriamycin resistant human breast adenocarcinoma cell line MCF-7/ADR, and compounds 1–2 were identified as potent low-cytotoxic MDR modulators with greater chemoreversal ability than the positive drug verapamilti.
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- 2021
4. Enantioselective Construction of 2-Aryl-2,3-dihydrobenzofuran Scaffolds Using Cu/SPDO-Catalyzed [3 + 2] Cycloaddition
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Ze-Ran Jing, Fu-Min Zhang, Dong-Dong Liang, Jin-Miao Tian, and Yong-Qiang Tu
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010405 organic chemistry ,Aryl ,Organic Chemistry ,Enantioselective synthesis ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Combinatorial chemistry ,Cycloaddition ,0104 chemical sciences ,Styrene ,Quinone ,Catalysis ,chemistry.chemical_compound ,chemistry ,Physical and Theoretical Chemistry - Abstract
A new, efficient approach toward the preparation of 2-aryl-2,3-dihydrobenzofuran scaffolds through the Cu/SPDO-catalyzed [3 + 2] cycloaddition between quinone ester and styrene derivatives has been developed. The procedure features excellent enantioselectivities (up to 99% ee), high yields (up to 96%), and broad substrate tolerance. Additionally, asymmetric synthesis of natural corsifurans A and B from commercially available starting materials has also been achieved in two or three steps using this reaction as a key transformation.
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- 2021
5. Catalytic Enantioselective Synthesis and Switchable Chiroptical Property of Inherently Chiral Macrocycles
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Q. L. Feng, Xin Zhang, Dong-Dong Liang, Jiang-Tao Li, Yan-E Zhang, Mei-Xiang Wang, Shuo Tong, and Jieping Zhu
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Macrocyclic Compounds ,Molecular Structure ,Chemistry ,Enantioselective synthesis ,Stereoisomerism ,General Chemistry ,Hydrogen-Ion Concentration ,Ligands ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Combinatorial chemistry ,Catalysis ,0104 chemical sciences ,Colloid and Surface Chemistry ,Enantiopure drug ,Coordination Complexes ,Intramolecular force ,Molecule ,Calixarenes ,Chirality (chemistry) ,Palladium - Abstract
We report herein a strategy to construct enantiopure inherently chiral macrocycles, ABCD-type heteracalix[4]-aromatics, through a catalytic enantioselective intramolecular C−N bond forming reaction. A chiral ligand-palladium complex was found to efficiently induce the inherent chirality of molecules during the macrocyclization process with ee values up to >99%. The resulting ABCD-type heteracalix[4]aromatics displayed excellent and pH triggered switchable electronic circular dichroism and circularly polarized luminescence properties.
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- 2020
6. Up-regulation of DcR3 in microbial toxins-stimulated HUVECs involves NF-κB signalling
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Hongwei Chen, Dong-Yu Liang, Yang Liu, Xiaoli Lou, and Yanqiang Hou
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Lipopolysaccharides ,0301 basic medicine ,Proline ,Lipopolysaccharide ,Pyridines ,lcsh:Animal biochemistry ,Pharmacology ,Biochemistry ,Jurkat cells ,Umbilical vein ,NF-κB ,Sepsis ,lcsh:Biochemistry ,Jurkat Cells ,03 medical and health sciences ,chemistry.chemical_compound ,Thiocarbamates ,Human Umbilical Vein Endothelial Cells ,medicine ,Humans ,lcsh:QD415-436 ,Protein Kinase Inhibitors ,Molecular Biology ,lcsh:QP501-801 ,HUVECs ,Anthracenes ,Receptors, Tumor Necrosis Factor, Member 6b ,Zymosan ,Imidazoles ,NF-kappa B ,medicine.disease ,Up-Regulation ,Teichoic Acids ,030104 developmental biology ,chemistry ,Lipoteichoic acid ,Decoy receptor 3 ,DcR3 ,Research Article ,Signal Transduction - Abstract
Background Sepsis is a severe condition characterised by the body’s systemic inflammatory response to infection. The specific sepsis-related biomarkers should be used in clinical diagnosis, therapeutic response monitoring, rational use of antibiotics, and prognosis (risk stratification), etc. Results In this study, we investigated the expression level of Decoy Receptor 3 (DcR3) and the mechanism of high expression in sepsis patients. Septic cell model experiments were performed by treating human umbilical vein endothelial cells (HUVECs) and Jurkat cells with lipopolysaccharide (LPS), lipoteichoic acid (LTA) and zymosan, respectively. SP600125, SB203580 and ammonium pyrrolidinedithiocarbamate (PDTC) were used to inhibit JNK1/2, p38MAPK and NF-κB signalling pathways in septic cell model, respectively. These results showed that DcR3 levels were higher in sepsis group than control. DcR3 mRNA and protein levels in HUVECs were increased following treatment with LPS, LTA and zymosan, and also increased in Jurkat cells treated by LPS, but not by LTA or zymosan. When HUVECs were treated with the NF-κB inhibitor PDTC, DcR3 expression was decreased compared with controls. However, SP600125 and SB203580 had no effect on DcR3 mRNA or protein levels. Conclusions The results indicated that DcR3 secretion proceeded through the NF-κB signalling pathway in HUVECs.
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- 2018
7. Effect of preservation time of formalin-fixed paraffin-embedded tissues on extractable DNA and RNA quantity
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Nai-Yan Zeng, Shuang Sha, Rong Yang, Qingqing Yi, Qing Chang, Junfeng Shi, and Dong-Yu Liang
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0301 basic medicine ,China ,Medicine (General) ,Time Factors ,Tissue Fixation ,storage time ,Formalin fixed paraffin embedded ,preservation ,DNA and RNA quantity ,Real-Time Polymerase Chain Reaction ,Biochemistry ,Specimen Handling ,FFPE tissues ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,R5-920 ,Formaldehyde ,Humans ,nucleic acid extraction ,Medicine ,Paraffin Embedding ,business.industry ,Gene Expression Profiling ,Biochemistry (medical) ,RNA ,DNA ,Cell Biology ,General Medicine ,Molecular biology ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,internal reference gene amplification ,business ,Retrospective Clinical Research Report - Abstract
Objectives This study aimed to investigate the factors affecting the quantity of DNA and RNA extractable from human formalin-fixed paraffin-embedded (FFPE) tissues stored for different lengths of time. Methods We randomly selected 20 FFPE specimens harvested from hysteromyoma patients with uterine fibroids during 2010, 2015, and 2017 at the Department of Pathology, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences. DNA and RNA extractions were performed using a DNA/RNA FFPE kit. DNA and RNA concentrations and their OD260/OD280 ratios were determined by a NanoDrop 2000 spectrophotometer. The human β-globin gene and aldehyde dehydrogenase-2 (ALDH2) gene were amplified from nucleic acids using a LightCycler 480 Real-Time PCR System, and PCR amplification products were electrophoresed on 1% agarose gels. Results Specimens that were stored for longer showed more degradation and a reduced concentration of DNA and RNA after nucleic acid extraction. However, there was no significant difference in DNA or RNA purity. β-globin and ALDH2 genes could be amplified from more than 99% of specimens. Conclusion We found that FFPE tissues stored for longer had a reduced quantity of extractable DNA and RNA. However, these tissues could be used for the analysis of some small target genes.
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- 2020
8. Preparation and antitumor effects of 4-amino-1,2,4-triazole Schiff base derivative
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Guo-Wei Jiang, Dong-Yu Liang, Yong-Jun Meng, Qing Chang, Yu-Ting Zhang, and Qingqing Yi
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4-amino-1,2,4-triazole Schiff base derivative ,Medicine (General) ,Cell Survival ,reduction ammonification reaction ,Antineoplastic Agents ,030204 cardiovascular system & hematology ,anticancer ,Biochemistry ,Pre-Clinical Research Report ,Nucleophilic substitution ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,R5-920 ,Cell Line, Tumor ,Humans ,Medicine ,MTT assay ,Schiff Bases ,Cell Proliferation ,Schiff base ,Dose-Response Relationship, Drug ,Triazines ,business.industry ,Biochemistry (medical) ,1,2,4-Triazole ,product characterization ,Cell Biology ,General Medicine ,Triazoles ,Combinatorial chemistry ,chemistry ,A549 Cells ,Benzaldehydes ,030220 oncology & carcinogenesis ,Hepatocytes ,business ,Derivative (chemistry) - Abstract
Objectives The purpose of this paper was to synthesize 4-amino-1,2,4-triazole Schiff base derivative and to evaluate its antitumor activity. Methods 2,4,6-Tris (4-formylphenoxy)-1,3,5-triazine was synthesized by nucleophilic substitution with reaction of p -hydroxybenzaldehyde with cyanuric chloride. Then, the intermediate was reacted with 1,2,4-triazole to form 4-amino-1,2,4-triazole Schiff base derivative by reduction and ammonification of aldehydes. The 4-amino-1,2,4-triazole Schiff base derivative was characterized by infrared spectroscopy, nuclear magnetic resonance, and elemental analyses. Finally, the anticancer effect of 4-amino-1,2,4-triazole Schiff base derivative was evaluated by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay on a lung adenocarcinoma cell line (A549) and a human hepatoma cell line (Bel7402). Results The product synthesized in this study was confirmed to be 4-amino-1,2,4-triazole Schiff base derivative, and it significantly suppressed the proliferation of cancer cell lines in a dose-dependent manner. Conclusions We successfully prepared 4-amino-1,2,4-triazole Schiff base derivative and verified its antitumor activity.
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- 2020
9. Liquid-like surface modification for effective anti-scaling membrane distillation with uncompromised flux
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Yuanyuan Zhang, Cheng-Hui Luo, Fangang Meng, Dong-Qing Liang, and Yu-Xi Huang
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Materials science ,Silanes ,Nanoparticle ,Filtration and Separation ,Membrane distillation ,Biochemistry ,Silane ,Polyvinylidene fluoride ,Surface coating ,chemistry.chemical_compound ,Membrane ,Chemical engineering ,chemistry ,Surface modification ,General Materials Science ,Physical and Theoretical Chemistry - Abstract
Membrane scaling is a critical challenge for membrane distillation (MD), especially when treating hypersaline brines. In this study, an anti-scaling membrane was developed with a liquid-like surface coating. This fabrication approach combined electrospun polyvinylidene fluoride (PVDF) membrane with surface fluorination without the addition of nanoparticles. Two fluoro silanes with the same alkyl-chain length but different hydrolysis reaction sites were investigated as the fluorination agents. Membrane characterizations indicated that surface modification with the single hydrolysis site fluoro silane (17-FAS-S) did not change the membrane morphology or structure. On the other hand, surface modification with the triple hydrolysis site fluoro silane (17-FAS-T) generated nanoparticles on the membrane surface, resulting in increased roughness. While both the 17-FAS-S and 17-FAS-T modified membranes exhibited excellent scaling resistance in the MD scaling tests, the 17-FAS-S membrane provided a much higher vapor flux than the 17-FAS-T one. Finally, the mechanism of scaling resistance and vapor permeability provided by the liquid-like modification was discussed.
- Published
- 2021
10. Polyfunctionalized biaryls accessed by a one-pot nucleophilic aromatic substitution and sigmatropic rearrangement reaction cascade under mild conditions
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Dong-Dong Liang, Shuo Tong, Shen-Yi Guo, and Mei-Xiang Wang
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010405 organic chemistry ,Carbazole ,Organic Chemistry ,Sigmatropic reaction ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Medicinal chemistry ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Nucleophilic aromatic substitution ,Drug Discovery ,Rearrangement reaction - Abstract
A practical synthetic method has been developed for polyfunctionalized biaryls based on a facile one-pot nucleophilic aromatic substitution (SNAr) reaction and [5,5]- or [3,3]-sigmatropic rearrangement reaction cascade. Under mild basic conditions, N-arylhydroxylamines reacted with o-activated fluoro (het)arenes to form N,O-diarylhydroxylamine intermediates which underwent spontaneously selective [5,5]-sigmatropic rearrangement reaction to produce diverse functionalized 4-amino-4′-hydroxy-1,1′-biaryls. A sequential SNAr reaction and [3,3]-sigmatropic rearrangement took place between N-arylhydroxylamines and 2-fluoropyridine derivatives or 4-fluorobenzonitrile to afford functionalized 2-amino-2′-hydroxy-1,1′-biaryls. As invaluable and unique building blocks, the resulting biaryls were applied in the straightforward synthesis of N2,O2-coronarene, carbazole, aza- and diaza carbazole derivatives.
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- 2021
11. Nod2–Rip2 Signaling Contributes to Intestinal Injury Induced by Muramyl Dipeptide Via Oligopeptide Transporter in Rats
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Hong-ze Zhang, Sheng-xia Wan, Jingquan Liu, Guoguang Ma, Zijun YinTao, Xiaoli Lou, Bin Shi, Yanqiang Hou, Dong-Yu Liang, and Wan-hua Yang
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Male ,Physiology ,Nod2 Signaling Adaptor Protein ,Inflammation ,Pharmacology ,Peptide Transporter 1 ,Rats, Sprague-Dawley ,Jejunum ,chemistry.chemical_compound ,Receptor-Interacting Protein Serine-Threonine Kinase 2 ,NOD2 ,parasitic diseases ,medicine ,Animals ,Intestinal Mucosa ,Oligopeptide ,Dipeptide ,Symporters ,biology ,Glycylglycine ,Chemistry ,Peptide transporter 1 ,NF-kappa B ,Gastroenterology ,Enteritis ,Small intestine ,body regions ,medicine.anatomical_structure ,Biochemistry ,biology.protein ,Cytokines ,Inflammation Mediators ,medicine.symptom ,Acetylmuramyl-Alanyl-Isoglutamine ,Muramyl dipeptide ,Signal Transduction - Abstract
PepT1 can transport bacterial oligopeptide products and induce intestinal inflammation. Our aim was to investigate the mechanism of the small intestine injury induced by bacterial oligopeptide product muramyl dipeptide (MDP) which is transported by PepT1. We perfused the jejunum with a solution with or without MDP, or with a solution of MDP + Gly-Gly and explored the degree of inflammation to determine the role of PepT1–Nod2 signaling pathway in small intestine mucosa. MDP perfusion induced inflammatory cell accumulation and intestinal damage, accompanied by an increase in mucosal Nod2 and Rip2 transcript expression. NFκB activity and inflammatory cytokine expression, including serum levels of TNF-α, IL-1β, and IL-6, increased in the MDP group compared to the controls; these effects were reversed by perfusion of the nutritional dipeptide Gly-Gly. MDP can be transported through PepT1, causing inflammatory damage in the rat small intestine. Nod2–Rip2–NFκB signaling involved in the small intestinal inflammatory injury caused by MDP which is transported through PepT1.
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- 2015
12. Terpenoids with alpha-glucosidase inhibitory activity from the submerged culture of Inonotus obliquus
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Lin-Yan Zhang, Dong-E Liang, Xia Zhang, Zha-Jun Zhan, Hai-Bo Bai, Lie-Feng Ma, Wei-Guang Shan, and You-Min Ying
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Stereochemistry ,Plant Science ,Fungus ,Horticulture ,Inhibitory postsynaptic potential ,Biochemistry ,Lanosterol ,chemistry.chemical_compound ,medicine ,Glycoside Hydrolase Inhibitors ,Nuclear Magnetic Resonance, Biomolecular ,Molecular Biology ,Acarbose ,Inotodiol ,Mushroom ,Molecular Structure ,biology ,alpha-Glucosidases ,General Medicine ,biology.organism_classification ,Terpenoid ,chemistry ,Alpha-glucosidase ,biology.protein ,Inonotus obliquus ,Agaricales ,Heterocyclic Compounds, 3-Ring ,medicine.drug - Abstract
Lanostane-type triterpenoids, inotolactones A and B, a drimane-type sesquiterpenoid, inotolactone C, and five known terpenoids 6β-hydroxy-trans-dihydroconfertifolin, inotodiol, 3β,22-dihydroxyanosta-7,9(11),24-triene, 3β-hydroxycinnamolide, and 17-hydroxy-ent-atisan-19-oic acid, were isolated from the submerged culture of chaga mushroom, Inonotus obliquus. Their structures were characterized by spectroscopic methods, including MS and NMR (1D and 2D) spectroscopic techniques. Inotolactones A and B, examples of lanostane-type triterpenoids bearing α,β-dimethyl, α,β-unsaturated δ-lactone side chains, exhibited more potent alpha-glucosidase inhibitory activities than the positive control acarbose. This finding might be related to the anti-hyperglycemic properties of the fungus and to its popular role as a diabetes treatment. In addition, a drimane-type sesquiterpenoid and an atisane-type diterpenoid were isolated from I. obliquus.
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- 2014
13. N-Bearing Furanone Derivatives from an Endophytic Fungus inHuperzia serrata
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Wei-Guang Shan, You-Min Ying, Dong-E Liang, Jian-Wei Wang, Jia-Gui Xiang, Zha-Jun Zhan, and Li-She Gan
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biology ,Stereochemistry ,Organic Chemistry ,Absolute configuration ,Huperzia serrata ,Endophytic fungus ,biology.organism_classification ,Biochemistry ,Endophyte ,Catalysis ,Inorganic Chemistry ,Peyronellaea sp ,Polyketide ,chemistry.chemical_compound ,Biosynthesis ,chemistry ,Drug Discovery ,Pyridine ,Physical and Theoretical Chemistry - Abstract
Two new polyketide derivatives, huaspenones C and D (1 and 2, resp.), were isolated from the cultures of an endophytic fungus Peyronellaea sp. HS-12, derived from the stems of Huperzia serrata. They share N-bearing furan-3(2H)-one backbone, and 2 has an unprecedented furo[3,2-c]pyridine skeleton. Their structures including the absolute configuration were elucidated by extensive spectroscopic analysis combined with quantum-chemical calculations. (2E,4E)-6-hydroxy-2-methylocta-2,4-dienoic acid (3), a key intermediate of the biosynthesis of 1 and 2, was also obtained from the endophyte.
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- 2013
14. Altered melatonin secretion and circadian gene expression with increased proinflammatory cytokine expression in early-stage sepsis patients
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Junlu Wang, Guohao Xie, William C. Cho, Cai-Xia Li, Xiangming Fang, Shuijing Wu, Baoli Cheng, Dong-Dong Liang, and QiXing Chen
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Period (gene) ,Biochemistry ,Proinflammatory cytokine ,Sepsis ,Melatonin ,Internal medicine ,Genetics ,medicine ,Humans ,Circadian rhythm ,Interleukin 6 ,Molecular Biology ,Aged ,biology ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Period Circadian Proteins ,Middle Aged ,medicine.disease ,Circadian Rhythm ,Cryptochromes ,Cytokine ,Endocrinology ,Gene Expression Regulation ,Oncology ,biology.protein ,Molecular Medicine ,Female ,Tumor necrosis factor alpha ,medicine.drug - Abstract
Inflammatory and immune responses, as well as melatonin secretion, are affected by circadian regulation. Abnormal circadian rhythm of melatonin release has been reported to be associated with the later stages of sepsis; however, its role in the early stages of sepsis is unclear. We studied 11 septic and 11 non-septic patients in our intensive care unit (ICU). Peripheral blood was drawn at 4-h intervals on the first day, beginning at 2:00 p.m., over a total period of 24 h. Plasma levels of melatonin, tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) were measured by radioimmunoassay or enzyme-linked immunosorbent assay (ELISA). Messenger RNA levels of circadian genes Cry-1 and Per-2 were analyzed using quantitative real-time PCR. Results show the circadian rhythm of melatonin secretion was altered in the early stages of sepsis. The melatonin secretion acrophase occurred earlier in septic patients at 6:00 p.m., compared with at 2:00 a.m. in non-septic ICU patients. Compared with the non-septic group, both Cry-1 and Per-2 expression were significantly decreased while TNF-α and IL-6 expression were significantly increased in septic patients [TNF-α, 64.1 (43.6-89.1) vs. 11.4 (10.4-12.5) ng/ml; IL-6, 41.2 (35.7-50.8) vs. 19.1 (16-136.7) ng/ml; median (range), both P=0.04]. The peak concentrations of TNF-α and IL-6 were shown to be in concordance with the rhythm of melatonin secretion. The circadian rhythm of melatonin secretion and circadian gene expression were altered in the early stages of sepsis, which likely led to the changes in pro-inflammatory cytokine release. These findings shed light on the potential link between circadian rhythm and the progression of early-stage sepsis.
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- 2013
15. ShDcR3 sensitizes TRAIL-resistant HCC cells by inducing caspase-dependent apoptosis while suppressing NF-κB dependent cFLIPL expression
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Qing Chang, Wei Huang, Dong-Yu Liang, and Yanqiang Hou
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0301 basic medicine ,Transcription, Genetic ,Protein Expression ,CASP8 and FADD-Like Apoptosis Regulating Protein ,lcsh:Medicine ,Apoptosis ,IκB kinase ,Biochemistry ,TNF-Related Apoptosis-Inducing Ligand ,0302 clinical medicine ,Cell Signaling ,Medicine and Health Sciences ,Cytotoxic T cell ,Small interfering RNAs ,Post-Translational Modification ,Phosphorylation ,lcsh:Science ,Apoptotic Signaling Cascade ,Multidisciplinary ,Cell Death ,Protein Kinase Signaling Cascade ,Chemistry ,Liver Diseases ,Liver Neoplasms ,NF-kappa B ,Signaling Cascades ,Nucleic acids ,Oncology ,Cell Processes ,Caspases ,030220 oncology & carcinogenesis ,Hyperexpression Techniques ,Research Article ,Signal Transduction ,Programmed cell death ,Carcinoma, Hepatocellular ,Down-Regulation ,Gastroenterology and Hepatology ,Research and Analysis Methods ,Carcinomas ,Caspase-Dependent Apoptosis ,03 medical and health sciences ,Downregulation and upregulation ,Cell Line, Tumor ,Gastrointestinal Tumors ,Gene Expression and Vector Techniques ,Genetics ,Humans ,Molecular Biology Techniques ,Non-coding RNA ,Molecular Biology ,Molecular Biology Assays and Analysis Techniques ,Cell growth ,Receptors, Tumor Necrosis Factor, Member 6b ,lcsh:R ,Biology and Life Sciences ,Cancers and Neoplasms ,Proteins ,Cell Biology ,Hepatocellular Carcinoma ,Gene regulation ,030104 developmental biology ,Cancer research ,RNA ,lcsh:Q ,Gene expression ,Decoy receptor 3 - Abstract
Evidence has shown that most hepatocellular carcinoma (HCC) cells are resistant to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. However, the molecular mechanisms underlying TRAIL-mediated apoptosis resistance are not well understood. In this study, we reported that downregulation of Decoy receptor 3 (DcR3) expression by lentiviral vectors carrying shRNA against DcR3 (LV-ShDcR3, shDcR3) in Huh7 both greatly enhanced TRAIL-mediated apoptosis and reduced cell proliferation capability. In addition, silencing DcR3 resulted in upregulation of the cell apoptotic regulators including Bid, caspase-3, and caspase-8. Caspase inhibitors inhibited shDcR3-mediated cell death, which indicated that downregulation of DcR3 expression in Huh7 cells increased TRAIL-induced caspase-dependent apoptotic cell death. Furthermore, although the knockdown of DcR3 altered the expression of some Bcl-2- and IAP-family proteins, this change was inhibited by pretreatment with a pancaspase inhibitor, which indicated the cytotoxic effect of shDcR3 was not due to the expression of these proteins. In contrast, shDcR3 significantly inhibited TRAIL-induced transcription factor nuclear κB (NF-κB) activation through the IκB kinase (IKK) pathway, as well as inhibited TRAIL-induced increases in FLICE-inhibitory protein long form (cFLIPL) expression at the transcriptional level. Silencing cFLIPL expression mimicked the cytotoxic effect of shDcR3 on TRAIL-mediated cell apoptosis. Moreover, overexpression of cFLIPL effectively prevented the increase in cell apoptosis in Huh7 cells co-treated with TRAIL and shDcR3. Taken together, our findings indicated that silencing DcR3 sensitizes TRAIL-mediated apoptosis in HCC cells by inhibiting NF-κB.
- Published
- 2018
16. Crystal structure of human phosphomavelonate kinase at 1.8 Å resolution
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Shenyan Gu, Xiao-Xue Yan, Jun-Feng Liu, Qing Chang, and Dong-Cai Liang
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Phosphotransferases (Phosphate Group Acceptor) ,Materials science ,Protein Conformation ,Kinase ,Resolution (electron density) ,Crystal structure ,Crystallography, X-Ray ,Biochemistry ,Catalysis ,law.invention ,Crystallography ,Protein structure ,Structural Biology ,law ,Catalytic Domain ,X-ray crystallography ,Humans ,Transferase ,Crystallization ,Molecular Biology - Published
- 2008
17. GSP-2, a polysaccharide extracted from Ganoderma sinense, is a novel toll-like receptor 4 agonist.
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Liu, Kai-Sheng, Zhang, Cheng, Dong, Hong-Liang, Li, Kai-Kai, Han, Quan-Bin, Wan, Yong, Chen, Rui, Yang, Fang, Li, Hai-Li, Ko, Chun-Hay, and Han, Xiao-Qiang
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TOLL-like receptors ,GANODERMA ,IMMUNOREGULATION ,CELLULAR recognition ,DEVELOPMENTAL biology ,MOLECULAR recognition - Abstract
Ganoderma sinense is a Chinese unique medicinal fungus that has been used in folk medicine for thousands of years. Polysaccharides are considered to be biologically active ingredients due to their immune-modulating functions. Previously we found that GSP-2, a new polysaccharide isolated from Ganoderma sinense, exerts an immunomodulatory effect in human peripheral blood mononuclear cells but the underlying mechanism is unclear. The present study aimed to investigate how GSP-2 triggers immunologic responses and the implicated signaling pathways. GSP-2 effects were investigated both in a macrophagic cell line, RAW264.7, and in primary macrophages. Moreover, the molecular basis of GSP-2 recognition by immune cells, and the consequent activation of signaling cascades, were explored by employing recombinant human HEK293-TLR-Blue clones, individually overexpressing various Toll-like receptors. GSP-2 dose-dependently induced the overexpression of Toll-like receptor 4 (TLR4) but did not affect the expression of other TLRs. Moreover, GSP-2 induced TNFα secretion in primary macrophages from wild-type, but not TLR4-knockout mice. In addition, GSP-2 upregulated TLR4 protein expression and activated the MAPK pathway in RAW246.7 macrophages. Finally, GSP-2 induced the production of the cytokines TNFα, IL1β, and IL6. Our data demonstrated that GSP-2 was specifically recognized by TLR4, promoting cytokine secretion and immune modulation in macrophages. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
18. Roscovitine Targets, Protein Kinases and Pyridoxal Kinase
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Olivier Lozach, Laurent Meijer, Sophie Schmitt, Flavio Meggio, Christoph Schächtele, Yongqin Wan, Amancio Carnero, Lin Tang, Frank Totzke, Stéphane Bach, Nathanael S. Gray, Stephen P. Coburn, Jens Reinhardt, Marcel Koken, Jean-Francois Dierick, Tao Jiang, Marie Knockaert, Lorenzo A. Pinna, Hervé Galons, Dong-Cai Liang, Blandine Baratte, Andrea S. Lerman, Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Mer et santé (MS), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Molécules et cibles thérapeutiques (MCT), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Indiana University - Purdue University Indianapolis (IUPUI), Indiana University System, Chinese Academy of Sciences [Beijing] (CAS), Laboratoire de Chimie Organique 2 Glycochimie (LCO2), Méthodologie de synthèse et molécules bioactives (MSMB), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Padova = University of Padua (Unipd), Centro Nacional de Investigaciones Oncologicas / Spanish National Cancer Research Centre [Madrid, Espagne] (CNIO), Genomics Institute of the Novartis Research Foundation, and Novartis Research Foundation
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Models, Molecular ,CDK ,[SDV]Life Sciences [q-bio] ,Molecular Conformation ,[CHIM.THER]Chemical Sciences/Medicinal Chemistry ,pharmacological selectivity ,Biochemistry ,Chromatography, Affinity ,CLK1 ,Mice ,chemistry.chemical_compound ,Adenosine Triphosphate ,0302 clinical medicine ,Tissue Distribution ,Pyridoxal Kinase ,Cells, Cultured ,Mice, Knockout ,chemistry.chemical_classification ,0303 health sciences ,Molecular Structure ,biology ,Kinase ,Cell Cycle ,Pyridoxal kinase ,3. Good health ,Cell biology ,cyclin-dependent kinase ,Pyridoxal Phosphate ,030220 oncology & carcinogenesis ,Protein kinase inhibitor ,Phosphorylation ,Pyridoxal ,Cell Survival ,Molecular Sequence Data ,Affinity chromatography ,03 medical and health sciences ,Cyclin-dependent kinase ,Roscovitine ,Animals ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Amino Acid Sequence ,Protein Kinase Inhibitors ,Molecular Biology ,Seliciclib ,030304 developmental biology ,Cyclin-dependent kinase 2 ,Cell Biology ,Fibroblasts ,Protein Structure, Tertiary ,Rats ,Enzyme ,chemistry ,Purines ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,biology.protein ,Protein Kinases - Abstract
International audience; Roscovitine (CYC202) is often referred to as a "selective inhibitor of cyclin-dependent kinases." Besides its use as a biological tool in cell cycle, neuronal functions, and apoptosis studies, it is currently evaluated as a potential drug to treat cancers, neurodegenerative diseases, viral infections, and glomerulonephritis. We have investigated the selectivity of (R)-roscovitine using three different methods: 1) testing on a wide panel of purified kinases that, along with previously published data, now reaches 151 kinases; 2) identifying roscovitine-binding proteins from various tissue and cell types following their affinity chromatography purification on immobilized roscovitine; 3) investigating the effects of roscovitine on cells deprived of one of its targets, CDK2. Altogether, the results show that (R)-roscovitine is rather selective for CDKs, in fact most kinases are not affected. However, it binds an unexpected, non-protein kinase target, pyridoxal kinase, the enzyme responsible for phosphorylation and activation of vitamin B 6. These results could help in interpreting the cellular actions of (R)-roscovitine but also in guiding the synthesis of more selective roscovitine analogs.
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- 2005
19. Crystal structure studies on rubrerythrin: enzymatic activity in relation to the zinc movement
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Jun Liao, Wenrui Chang, Dong-Cai Liang, Jiping Zhang, Mei Li, Tao Jiang, Ming-Yih Liu, Lulu Gui, and Jean LeGall
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Models, Molecular ,Iron ,chemistry.chemical_element ,Rubrerythrin ,Zinc ,Crystal structure ,Crystallography, X-Ray ,Biochemistry ,Inorganic Chemistry ,Crystal ,Metal ,chemistry.chemical_compound ,Bacterial Proteins ,Molecule ,Desulfovibrio vulgaris ,Pyrophosphatases ,biology ,Rubredoxins ,biology.organism_classification ,Hemerythrin ,Crystallography ,Monomer ,chemistry ,visual_art ,visual_art.visual_art_medium ,Ferredoxins ,Dimerization ,Oxidation-Reduction - Abstract
Rubrerythrin (Rr) is a non-heme iron protein isolated from anaerobic sulfate-reducing bacteria. Rr is a dimeric molecule, each monomer contains a Fe(SCys)4 center in the C-terminal domain and a binuclear metal center in the N-terminal domain. Rr structures with different protein sources and/or preparation procedures have been studied. Two Rr crystal structures have been solved with significant differences in their binuclear metal centers. The first structure, which was obtained from expressed protein under aerobic conditions, has a diiron–oxo center. The second structure, which was obtained from native protein of Desulfovibrio vulgaris under aerobic conditions, has an Fe–Zn center with the zinc position differing from the corresponding iron position in the former structure by approximately 2 A. The crystal structures of Rr isolated from D. vulgaris (Hildenborough, NCIB 8303), the same as the second structured but prepared under anaerobic conditions, are reported in this paper. The binuclear metal center in these structures is an Fe–Zn center. When the crystal was exposed to air, the zinc atom moved gradually, approximately 2 A, accompanied by the entrance of a water molecule (or hydroxyl group) and changes in the binuclear metal center microenvironment. This finding can explain the differences between the two different structures. The results suggest that the zinc movement may be related to the enzymatic activity of Rr. Electronic supplementary material is available if you access this article at http://dx.doi.org/10.1007/s00775-002-0400-0. On that page (frame on the left side), a link takes you directly to the supplementary material.
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- 2003
20. Preliminary crystallographic studies of two C-terminally truncated copper-containing nitrite reductases from Achromobacter cycloclastes: changed crystallizing behaviors caused by residue deletion
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Ming Yih Liu, Dong Cai Liang, Xiao Min An, Wenrui Chang, Jiping Zhang, Haitao Li, Tschining Chang, Lu Lu Gui, and Jean Le Gall
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Models, Molecular ,Nitrite Reductases ,Stereochemistry ,Mutant ,Biophysics ,chemistry.chemical_element ,Crystallography, X-Ray ,Biochemistry ,Residue (chemistry) ,Alcaligenes ,Molecular Biology ,Sequence Deletion ,chemistry.chemical_classification ,biology ,Cell Biology ,Nitrite reductase ,Copper ,Enzyme assay ,Crystallography ,Enzyme ,chemistry ,biology.protein ,Protein quaternary structure ,Crystallization ,Monoclinic crystal system - Abstract
The C-terminal segment of copper-containing nitrite reductase from Achromobacter cycloclastes (AcNiR) has been found essential for maintaining both the quaternary structure and the enzyme activity of AcNiR. C-terminal despentapeptide AcNiR (NiRc-5) and desundecapeptide AcNiR (NiRc-11) are two important truncated mutants whose activities and stability have been affected by residue deletion. In this study, the two mutants were crystallized using the hanging drop vapor diffusion method. Crystals of NiRc-5 obtained at pH 5.0 and 6.2 both belonged to the P2(1)2(1)2(1) space group with unit cell parameters a=99.0 A, b=117.4 A, c=122.8 A (pH 5.0) and a=98.9A, b=117.7A, c=123.0A (pH 6.2). NiRc-11 was crystallized in two crystal forms: the tetragonal form belonged to the space group P4(1) with a=b=96.0A and c=146.6A; the monoclinic form belonged to the space group P2(1) with a=86.0A, b=110.1A, c=122.7A, and beta=101.9 degrees. The crystallizing behaviors of the two mutants differed from that of the native enzyme. Such change in combination with residue deletion is also discussed here.
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- 2002
21. Crystal Structure of Brain Pyridoxal Kinase, a Novel Member of the Ribokinase Superfamily
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Francis Kwok, Minghui Li, Samuel Chun-Lap Lo, Chi-Kong Lau, Jiping Zhang, Tao Jiang, Dong-Cai Liang, and Wenrui Chang
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Models, Molecular ,Binding Sites ,Pyridoxal ,Sheep ,biology ,Protein Conformation ,Stereochemistry ,Kinase ,Brain ,Active site ,Cell Biology ,Crystallography, X-Ray ,Biochemistry ,Pyridoxal kinase ,Phosphotransferases (Alcohol Group Acceptor) ,Protein structure ,ATP hydrolysis ,biology.protein ,Animals ,Transferase ,Binding site ,Ribokinase ,Pyridoxal Kinase ,Molecular Biology - Abstract
The three-dimensional structures of brain pyridoxal kinase and its complex with the nucleotide ATP have been elucidated in the dimeric form at 2.1 and 2.6 A, respectively. Results have shown that pyridoxal kinase, as an enzyme obeying random sequential kinetics in catalysis, does not possess a lid shape structure common to all kinases in the ribokinase superfamily. This finding has been shown to be in line with the condition that pyridoxal kinase binds substrates with variable sizes of chemical groups at position 4 of vitamin B(6) and its derivatives. In addition, the enzyme contains a 12-residue peptide loop in the active site for the prevention of premature hydrolysis of ATP. Conserved amino acid residues Asp(118) and Tyr(127) in the peptide loop could be moved to a position covering the nucleotide after its binding so that its chance to hydrolyze in the aqueous environment of the active site was reduced. With respect to the evolutionary trend of kinase enzymes, the existence of this loop in pyridoxal kinase could be classified as an independent category in the ribokinase superfamily according to the structural feature found and mechanism followed in catalysis.
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- 2002
22. Three-dimensional structure of manganese superoxide dismutase from Bacillus halodenitrificans, a component of the so-called 'green protein'
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Tschining Chang, Jiping Zhang, Jean Le Gall, Jun Liao, Mei Li, Tao Jiang, Ming Yih Liu, Dong Cai Liang, Wenrui Chang, and Lu Lu Gui
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Models, Molecular ,Denitrification ,animal diseases ,Molecular Sequence Data ,Static Electricity ,chemistry.chemical_element ,Bacillus ,Manganese ,Crystallography, X-Ray ,Catalysis ,Structure-Activity Relationship ,Bacterial Proteins ,Structural Biology ,Oxidoreductase ,Amino Acid Sequence ,Protein Structure, Quaternary ,chemistry.chemical_classification ,Binding Sites ,Sequence Homology, Amino Acid ,Superoxide Dismutase ,Chemistry ,fungi ,Substrate (chemistry) ,Nucleoside-diphosphate kinase ,Halophile ,Zinc ,Biochemistry ,Cytoplasm ,Salts - Abstract
A so-called "green protein" has been purified from a moderate halophilic eubacterium, Bacillus halodenitrificans (ATCC 49067), under anaerobic conditions. The protein, which might play an important role in denitrification, dissociates mainly into two components after exposure to air: a manganese superoxide dismutase (GP-MnSOD) and a nucleoside diphosphate kinase. As a first step in elucidating the overall structure of the green protein and the role of each component, the 2.8-A resolution crystal structure of GP-MnSOD was determined. Compared with other manganese dismutases, GP-MnSOD shows two significant characteristics. The first is that the entrance to its substrate channel has an additional basic residue-Lys38. The second is that its surface is decorated with an excess of acidic over basic residues. All these structural features may be related to GP-MnSOD's high catalytic activity and its endurance against the special cytoplasm of B. halodenitrificans. The structure of GP-MnSOD provides the basis for recognizing its possible role and assembly state in the green protein.
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- 2002
23. Structural and functional characterization of Cys4 zinc finger motif in the recombination mediator protein RecR
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Qun Tang, Yan-Ping Liu, Xiao-Xue Yan, and Dong-Cai Liang
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Models, Molecular ,DNA Repair ,Protein Conformation ,Protein domain ,Molecular Sequence Data ,Thermoanaerobacter ,Plasma protein binding ,Biology ,Crystallography, X-Ray ,Biochemistry ,Protein structure ,Bacterial Proteins ,Amino Acid Sequence ,Cysteine ,Molecular Biology ,LIM domain ,Zinc finger ,Genetics ,Zinc Fingers ,Cell Biology ,DNA ,Zinc finger nuclease ,Cell biology ,RING finger domain ,PHD finger ,Mutation - Abstract
Zinc finger motif widely exists in protein structure, which can play different roles in different proteins. RecR is an important recombination mediator protein (RMP) in the RecFOR pathway and zinc finger motif is the most conserved domain in RecR protein. However, the function of this zinc finger motif in RecR is unclear. Here, we have studied the structures of the single cysteine and double cysteines mutation within the zinc finger motif in Thermoanaerobacter tengcongensis RecR (TTERecR). We have also studied the DNA binding ability as well as TTERecO protein binding ability of single, double and even triple cysteines mutation of the zinc finger motif, and the mutants do not alter DNA binding by RecR nor the interaction between RecR and RecO. The function of TTERecR zinc finger motif is to maintain the stability of the three-dimensional structure.
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- 2014
24. Contributory presentations/posters
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N. Manoj, V. R. Srinivas, A. Surolia, M. Vijayan, K. Suguna, R. Ravishankar, R. Schwarzenbacher, K. Zeth, null Diederichs, G. M. Kostner, A. Gries, P. Laggner, R. Prassl, null Madhusudan, Pearl Akamine, Nguyen-huu Xuong, Susan S. Taylor, M. Bidva Sagar, K. Saikrishnan, S. Roy, K. Purnapatre, P. Handa, U. Varshney, B. K. Biswal, N. Sukumar, J. K. Mohana Rao, A. Johnson, Vasantha Pattabhi, S. Sri Krishna, Mira Sastri, H. S. Savithri, M. R. N. Murthy, Bindu Pillai, null Kannan, M. V. Hosur, Mukesh Kumar, Swati Patwardhan, K. K. Kannan, B. Padmanabhaa, S. Sasaki-Sugio, M. Nukaga, T. Matsuzaki, S. Karthikevan, S. Sharma, A. K. Sharma, M. Paramasivam, P. Kumar, J. A. Khan, S. Yadav, A. Srinivasan, T. P. Singh, S. Gourinath, Neelima Alam, A. Srintvasan, Vikas Chandra, Punit Kaur, Ch. Betzel, S. Ghosh, A. K. Bera, S. Bhattacharya, S. Chakraborty, A. K. Pal, B. P. Mukhopadhyay, I. Dey, U. Haldar, Asok Baneriee, Jozef Sevcik, Adriana Solovicova, K. Sekar, M. Sundaralingam, N. Genov, Dong-cai Liang, Tao Jiang, Ji-ping Zhang, Wen-rui Chang, Wolfgang Jahnke, Marcel Blommers, S. C. Panchal, R. V. Hosur, Bindu Pillay, Puniti Mathur, S. Srivatsun, Ratan Mani Joshi, N. R. Jaganathan, V. S. Chauhan, H. S. Atreya, S. C. Sahu, K. V. R. Chary, Girjesh Govil, Elisabeth Adjadj, Éric Quinjou, Nadia Izadi-Pruneyre, Yves Blouquit, Joël Mispelter, Bernadette Heyd, Guilhem Lerat, Philippe Milnard, Michel Desmadreil, Y. Lin, B. D. Nageswara Rao, Vidva Raghunathan, Mei H. Chau, Prashant Pesais, Sudha Srivastava, Evans Coutinho, Anil Saran, Leizl F. Sapico, Jayson Gesme, Herbert Lijima, Raymond Paxton, Thamarapu Srikrishnan, C. R. Grace, G. Nagenagowda, A. M. Lynn, Sudha M. Cowsik, Sarata C. Sahu, S. Chauhan, A. Bhattacharya, G. Govil, Anil Kumar, Maurizio Pellecchia, Erik R. P. Zuiderweg, Keiichi Kawano, Tomoyasu Aizawa, Naoki Fujitani, Yoichi Hayakawa, Atsushi Ohnishi, Tadayasu Ohkubo, Yasuhiro Kumaki, Kunio Hikichi, Katsutoshi Nitta, V. Rani Parvathy, R. M. Kini, Takumi Koshiba, Yoshihiro Kobashigawa, Min Yao, Makoto Demura, Astushi Nakagawa, Isao Tanaka, Kunihiro Kuwajima, Jens Linge, Seán O. Donoghue, Michael Nilges, G. Chakshusmathi, Girish S. Ratnaparkhi, P. K. Madhu, R. Varadarajan, C. Tetreau, M. Tourbez, D. Lavalette, M. Manno, P. L. San Biagio, V. Martorana, A. Emanuele, S. M. Vaiana, D. Bulone, M. B. Palma-Vittorelli, M. U. Palma, V. D. Trivedi, S. F. Cheng, W. J. Chien, S. H. Yang, S. Francis, D. K. Chang, Renn Batra, Michael A. Geeves, Dietmar J. Manstein, Joanna Trvlska, Pawel Grochowski, Maciej Geller, K. Ginalski, P. Grochowski, B. Lesyng, P. Lavalette, Y. Blouquit, D. Roccatano, A. Amadei, A. Di Nola, H. J. C. Berendsen, Bosco Ho, P. M. G. Curmi, H. Berry, D. Lairez, E. Pauthe, J. Pelta, V. Kothekar, Shakti Sahi, M. Srinivasan, Anil K. Singh, Kartha S. Madhusudnan, Fateh S. Nandel, Harpreet Kaur, Balwinder Singh, D. V. S. Jain, K. Anton Feenstra, Herman J. C. Berendsen, F. Tama, Y. -H. Sanejouand, N. Go, Deepak Sharma, Sunita Sharma, Santosh Pasha, Samir K. Brahmachari, R. Viiavaraghavan, Jyoti Makker, Sharmisllia Dey, S. Kumar, G. S. Lakshmikanth, G. Krishnamoorthy, V. M. Mazhul, E. M. Zaitseva, Borys Kierdaszuk, J. Widengren, B. Terry, Ü. Mets, R. Rigler, R. Swaminathan, S. Thamotharan, N. Yathindra, Y. Shibata, H. Chosrowjan, N. Mataga, I. Morisima, Tania Chakraharty, Ming Xiao, Roger Cooke, Paul Selvin, C. Branca, A. Faraone, S. Magazù, G. Maisano, P. Migliardo, V. Villari, Digambar V. Behere, M. Sharique Zahida Waheed Deva, M. Brunori, F. Cutruzzolà, Q. H. Gibson, C. Savino, C. Travaglini-Allocatelli, B. Vallone, Swati Prasad, Shyamalava Mazumdar, Samaresh Mitra, P. Soto, R. Fayad, I. E. Sukovataya, N. A. Tyulkova, Sh. V. Mamedov, B. Aktas, M. Canturk, B. Aksakal, R. Yilgin, K. I. Bogutska, N. S. Miroshnichenko, S. Chacko, M. DiSanto, J. A. Hypolite, Y-M. Zheng, A. J. Wein, M. Wojciechowski, T. Grycuk, J. Antosiewicz, Marc A. Ceruso, Alfredo Di Nola, Subhasis Bandvopadhvay, Bishnu P. Chatterjee, Devapriva Choudhury, Andrew Thompson, Vivian Stojanoff, Jerome Pinkner, Scott Hultgren, Stefan Khight, Delphine Flatters, Julia Goodfellow, Fumi Takazawatt, Minoru Kanehisa, Masaki Sasai, Hironori Nakamura, Wang Bao Han, Yuan Zheng, Wang Zhi Xin, Pan xin Min, Vlnod Bhakuni, Sangeeta Kulkarni, Atta Ahmad, Koodathingal Prakash, Shashi Prajapati, Alexey Surin, Tomoharu Matsumoto, Li Yang, Yuki Nakagawa, Kazumoto Kimura, Yoshiyuki Amemiya, Gennady V. Semisotnov, Hiroshi Kihara, Saad Tayyab, Salman Muzammil, Yogesh Kumar, Vinod Bhakuni, Monica Sundd, Suman Kundu, M. V. Jagannadham, Medicherla V. Jagannadham, Bina Chandani, Ruby Dhar, Lalankumar Sinha, Deepti Warrier, Sonam Mehrotra, Purnima Khandelwal, Subhendu Seth, Y. U. Sasidhar, C. Ratna Prabha, Arun Gidwani, K. P. Madhusudan, Akira R. Kinjo, Ken Nishikawa, Suvobrata Chakravarty, Raghavan Varadarajan, K. Noyelle, P. Haezebrouck, M. Joniau, H. Van Dael, Sheffali Dash, Indra Brata Jha, Rajiv Bhat, Prasanna Mohanty, A. K. Bandyopadhyay, H. M. Sonawat, Ch. Mohan Rao, Siddhartha Datta, K. Rajaraman, B. Raman, T. Ramakrishna, A. Pande, J. Pande, S. Betts, N. Asherie, O. Ogun, J. King, G. Benedek, I. V. Sokolova, G. S. Kalacheva, Masashi Sonoyama, Yasunori Yokoyama, Kunihiro Taira, Shigeki Mitaku, Chicko Nakazawal, Takanori Sasakil, Yuri Mukai, Naoki Kamo, Seema Dalal, Lynne Regan, Shigeki Mituku, Mihir Roychoudhury, Devesh Kumar, Dénes Lőrinczv, Franciska Könczöl, László Farkas, Joseph Belagyi, Christoph Schick, Christy A. Thomson, Vettai S. Ananthanarayanan, E. G. Alirzayeva, S. N. Baba-Zade, M. Michael Gromiha, M. Oobatake, H. Kono, J. An, H. Uedaira, A. Sarai, Kazufumi Takano, Yuriko Yamagata, Katsuhide Yutani, Gouri S. Jas, Victor Muñoz, James Hofrichter, William A. Eaton, Jonathan Penoyar, Philip T. Lo Verde, J. Kardos, Á. Bódi, I. Venekei, P. Závodszky, L. Gráf, András Szilágyi, Péter Závodszky, R. D. Allan, J. Walshaw, D. N. Woolfson, Jun Funahashi, Savan Gupta, M. Mangoni, P. Roccatano, Gosu Ramachandraiah, Nagasuma R. Chandra, Barbara Ciani, Derek N. Woolfson, Usha B. Nair, Kanwal J. Kaur, Dinakar M. Salunke, Chittoor P. Swaminathan, Avadhesha Surolia, A. Pramanik, P. Jonasson, G. Kratz, O. T. Jansson, P. -Å. Nygren, S. Ståhl, K. Ekberg, B. -L. Johansson, S. Uhlén, M. Uhlén, H. Jörnvall, J. Wahren, Karin Welfle, Rolf Misselwitz, Wolfgang Höhne, Heinz Welfle, L. G. Mitskevich, N. V. Fedurkina, B. I. Kurganov, Gotam K. Jarori, Haripada Maity, J. Guharay, B. Sengupta, P. K. Sengupta, K. Sridevi, S. R. Kasturi, S. P. Gupta, Gunjan Agarwal, Suzanne Kwong, Robin W. Briehl, O. I. Ismailova, N, A. Tyulkova, C. Hariharan, D. Pines, E. Pines, M. Zamai, R. Cohen-Luria, A. Yayon, A. H. Parola, M. J. Padya, G. A. Spooner, D. N. Woolfeon, Panchan Bakshi, D. K. Bharadwaj, U. Sharma, N. Srivastava, R. Barthwal, N. R. Jagannathan, Keiko Matsuda, Takaaki Nishioka, Nobuhiro Go, T. Aita, S. Urata, Y. Husimi, Mainak Majumder, Nicola G. A. Abrescia, Lucy Malinina, Juan A. Subirana, Juan Aymami, Ramón Eritxa, Miquel Coll, B. J. Premraj, R. Thenmalarchelvi, P. Satheesh Kumar, N. Gautham, Lou -Sing Kan, null Ming-Hou, Shwu-Bin Lin, Tapas Sana, Kanal B. Roy, N. Bruant, D. Flatters, R. Lavery, D. Genest, Remo Rons, Heinz Sklenar, Richard Lavery, Sudip Kundu, Dhananjay Bhattacharyya, Debashree Bandyopadhyay, Ashoke Ranjan Thakur, Rabi Majumdar, F. Barceló, J. Portugal, Sunita Ramanathan, B. J. Rao, Mahua Gliosli, N. Vinay Kumar, Umesh Varshney, Shashank S. Pataskar, R. Sarojini, S. Selvasekarapandian, P. Kolandaivel, S. Sukumar, P. Kolmdaivel, Motilal Maiti, Anjana Sen, Suman Das, Elisa Del Terra, Chiara Suraci, Silvia Diviacco, Franco Quadrifoglio, Luigi Xodo, Arghya Ray, G. Karthikeyan, Kandala V. R. Chary, Basuthkar J. Rao, Anwer Mujeeb, Thomas L. James, N. Kasyanenko, E. E. F. Haya, A. Bogdanov, A. Zanina, M. R. Bugs, M. L. Cornélio, M. Ye. Tolstorukov, Nitish K. Sanval, S. N. Tiwari, Nitish K. Sanyal, Mihir Roy Choudhury, P. K. Patel, Neel S. Bhavesh, Anna Gabrielian, Stefan Wennmalm, Lars Edman, Rudolf Rigler, B. Constantinescu, L. Radu, I. Radulcscu, D. Gazdaru, Sebastian Wärmländer, Mikael Leijon, Setsuyuki Aoki, Takao Kondo, Masahiro Ishiura, V. A. Pashinskaya, M. V. Kosevich, V. S. Shelkovsky, Yu. P. Blagoy, Ji-hua Wang, R. Malathi, K. Chandrasekhar, E. R. Kandimalla, S. Agrawal, V. K. Rastogi, M. Alcolea Palafox, Chatar Singh, A. D. Beniaminov, S. A. Bondarenko, E. M. Zdobnov, E. E. Minyat, N. B. Ulyanov, V. I. Ivanov, J. S. Singh, Kailas D. Sonawane, Henri Grosjean, Ravindra Tewari, Uddhavesh B. Sonavane, Annie Morin, Elizabeth A. Doherty, Jennifer A. Doudna, H. Tochio, S. Sato, H. Matsuo, M. Shirakawa, Y. Kyogoku, B. Javaram, Surjit B. Dixit, Piyush Shukla, Parul Kalra, Achintya Das, Kevin McConnell, David L. Beveridge, W. H. Sawyer, R. Y. S. Chan, J. F. Eccelston, Yuling Yan, B. E. Davidson, Eimer Tuite, Bengt Norden, Peter Nielsen, Masayuki Takahashi, Anirban Ghosh, Manju Bansal, Frauke Christ, Hubert Thole, Wolfgang Wende, Alfred Pingoud, Vera Pingoud, Pratibha Mehta Luthra, Ramesh Chandra, Ranjan Sen, Rodney King, Robert Weisberg, Olaf F. A. Larsen, Jos Berends, Hans A. Heus, Cornelis W. Hilbers, Ivo H. M. van Stokkum, Bas Gobets, Rienk van Grondelle, Herbert van Amerongen, HE. Sngrvan, Yu. S. Babayan, N. V. Khudaverdian, M. Gromiha, F. Pichierri, M. Aida, P. Prabakaran, K. Sayano, Saulius Serva, Eglė Merkienė, Giedrius Vilkaitis, Elmar Weinhold, Saulius Klimašauskas, Eleonora Marsich, Antonella Bandiera, Giorgio Manzini, G. Potikyan, V. Arakelyan, Yu. Babayan, Alex Ninaber, Julia M. Goodfellow, Yoichiro Ito, Shigeru Ohta, Yuzuru Husimi, J. Usukura, H. Tagami, H. Aiba, Mougli Suarez, Elia Nunes, Deborah Keszenman, E. Carmen Candreva, Per Thyberg, Zeno Földes-Papp, Amita Joshi, Dinesh Singh, M. R. Rajeswari, null Ira, M. Pregetter, H. Amenitsch, J. Chapman, B. N. Pandev, K. P. Mishra, E. E. Pohl, J. Sun, I. I. Agapov, A. G. Tonevitsky, P. Pohl, S. M. Dennison, G. P. Gorbeako, T. S. Dynbko, N. Pappavee, A. K. Mishra, Prieto Manuel, Almeida Rodrigo, Loura Luis, L. Ya. Gendel, S. Przestalski, J. Kuczera, H. Kleszczyńska, T. Kral, E. A. Chernitsky, O. A. Senkovich, V. V. Rosin, Y. M. Allakhverdieva, G. C. Papageorgiou, R. A. Gasanov, Calin Apetrei, Tudor Savopol, Marius Balea, D. Cucu, D. Mihailescu, K. V. Ramanathan, Goran Bačić, Nicolas Sajot, Norbert Garnier, Serge Crouzy, Monique Genest, Z. S. Várkonyi, O. Zsiros, T. Farkas, Z. Combos, Sophie Cribier, I. F. Fraceto, S. Schreier, A. Spisni, F. de Paula, F. Sevšek, G. Gomišček, V. Arrigler, S. Svetina, B. Žekš, Fumimasa Nomura, Miki Nagata, Kingo Takiguchi, Hirokazu Hotani, Lata Panicker, P. S. Parvathanathan, A. Ishino, A. Saitoh, H. Hotani, K. Takiguchi, S. Afonin, A. Takahashi, Y. Nakato, T. Takizawa, Dipti Marathe, Kent Jørgensen, Satinder S. Rawat, R. Rukmini, Amitabha Chattopadhyay, M. Šentiurc, J. Štrancar, Z. Stolič, K. Filipin, S. Pečar, S. C. Biswas, Satyen Sana, Anunay Samanta, Koji Kinoshita, Masahito Yamazaki, Tetsuhiko Ohba, Tai Kiuchi, null Yoshitoshi, null Kamakura, Akira Goto, Takaaki Kumeta, Kazuo Ohki, I. P. Sugar, T. E. Thompson, K. K. Thompson, R. L. Biltonen, Y. Suezaki, H. Ichinose, M. Akivama, S. Matuoka, K. Tsuchihashi, S. Gasa, P. Mattjus, J. G. Molotkovsky, H. M. Pike, R. E. Brown, Ashish Arora, Jörg H. Kleinschmidt, Lukas K. Tamm, O. G. Luneva, K. E. Kruglyakova, V. A. Fedin, O. S. Kuptsoya, J. W. Borst, N. V. Visser, A. J. W. G. Visser, T. S. Dyubko, Toshihiko Ogihara, Kiyoshi Mishima, A. L. Shvaleva, N. Č. Radenović, P. M. Minić, M. G. Jeremić, Č. N. Radenović, T. F. Aripov, E. T. Tadjibaeva, O. N. Vagina, M. V. Zamaraeva, B. A. Salakhutdinov, A. Cole, M. Poppofl, C. Naylor, R. Titball, A. K. Basak, J. T. Eaton, C. E. Naylor, N. Justin, D. S. Moss, R. W. Titball, F. Nomura, M. Nagata, S. Ishjkawa, S. Takahashi, Kaoru Obuchi, Erich Staudegger, Manfred Kriechbaum, Robert I. Lehrer, Alan J. Waring, Karl Lohner, Susanne Gangl, Bernd Mayer, Gottfried Köhler, J. Shobini, Z. Guttenberg, B. Lortz, B. Hu, E. Sackmann, N. M. Kozlova, L. M. Lukyanenko, A. N. Antonovich, E. I. Slobozhanina, Andrey V. Krylov, Yuri N. Antonenko, Elena A. Kotova, Alexander A. Yaroslavov, Subhendu Ghosh, Amal K. Bera, Sudipto Das, Eva Urbánková, Masood Jelokhani-Niaraki, Karl Freeman, Petr Jezek, P. B. Usmanov, A. Ongarbaev, A. K. Tonkikh, Peter Pohl, Sapar M. Saparov, P. Harikumar, J. P. Reeves, S. Rao, S. K. Sikdar, A. S. Ghatpande, C. Corsso, A. C. Campos de Carvalho, W. A. Varanda, C. ElHamel, E. Dé, N. Saint, G. Molle, Anurae Varshney, M. K. Mathew, E. Loots, E. Y. Isacoff, Michiki Kasai, Naohiro Yamaguchi, Paramita Ghosh, Joseph Tigyi, Gabor Tigyi, Karoly Liliom, Ricardo Miledi, Maja R. Djurisic, Pavle R. Andjus, Indira H. Shrivastava, M. S. P. Sansom, C. Barrias, P. F. Oliveira, A. C. Mauricio, A. M. Rebelo da Costa, I. A. Lopes, S. V. Fedorovich, V. S. Chubanov, M. V. Sholukh, S. V. Konev, N. Fedirko, V. Manko, M. Klevets, N. Shvinka, B. S. Prabhananda, Mamata H. Kombrabail, S. Aravamudhan, Berenice Venegas-Cotero, Ivan Ortega Blake, Zhi-hong Zhang, Xiao-jian Hu, Han-qing Zhou, Wei-ying Cheng, Hang-fang Feng, L. O. Dubitsky, L. S. Vovkanvch, I. A. Zalyvsky, E. Savio-Galimberti, P. Bonazzola, J. E. Ponce-Homos, Mario Parisi, Claudia Capurro, Roxana Toriano, Laxma G. Ready, Larry R. Jones, David D. Thomas, B. A. Tashmukhamedov, B. T. Sagdullaev, D. Heitzmann, R. Warth, M. Bleich, R. Greger, K. T. G. Ferreira, H. G. Ferreira, Orna Zagoory, Essa Alfahel, Abraham H. Parola, Zvi Priel, H. Hama-Inaba, R. Wang, K. Choi, T. Nakajima, K. Haginoya, M. Mori, H. Ohyama, O. Yukawa, I. Hayata, Nanda B. Joshi, Sridhar K. Kannurpatti, Preeti G. Joshi, Mau Sinha, Xun Shen, Tianhui Hu, Ling Bei, Menno L. W. Knetsch, Nicole Schäfers, John Sandblom, Juris Galvanovskis, Roxana Pologea-Moraru, Eugenia Kovacs, Alexandra Dinu, S. H. Sanghvi, V. Jazbinšek, G. Thiel, W. Müller, G. Wübeller, Z. Tronteli, Leš Fajmut, Marko Marhl, Milan Brumen, I. D. Volotovski, S. G. Sokolovski, M. R. Knight, Alexei N. Vasil’ev, Alexander V. Chalyi, P. Sharma, P. J. Steinbach, M. Sharma, N. D. Amin, J. Barchir, R. W. Albers, H. C. Pant, M. Balasubramanyam, M. Condrescu, J. P. Gardner, Shamci Monajembashi, Gotz Pilarczyk, K. O. Greulich, F. M. El-Refaei, M. M. Talaat, A. I. El-Awadi, F. M. Ali, Ivan Tahradník, Jana Pavelková, Alexandra Zahradniková, Boris S. Zhorov, Vettai S. Ananthanaravanan, M. Ch. Michailov, E. Neu, W. Seidenbusch, E. Gornik, D. Martin, U. Welscher, D. G. Weiss, B. R. Pattnaik, A. Jellali, V. Forster, D. Hicks, J. Sahel, H. Dreyfus, S. Picaud, Hong-Wei Wang, Sen-fang Sui, Pradeep K. Luther, John Barry, Ed Morris, John Squire, C. Sivakama Sundari, D. Balasubramanian, K. Veluraia, T. Hema Thanka Christlet, M. Xavier Suresh, V. Laretta-Garde, Dubravka Krilov, Nataša Stojanović, Janko N. Herak, Ravi Jasuja, Maria Ivanova, Rossen Mirchev, Frank A. Ferrone, David Stopar, Ruud B. Spruijt, Cor J. A. M. Wolfs, Marcus A. Hemminga, G. Arcovito, M. De Spirito, Rajendra K. Agrawal, Amy B. Heagle, Pawel Penczek, Robert Grassucci, Joachim Frank, Manjuli R. Sharma, Loice H. Jeyakumar, Sidney Fleischer, Terence Wagenknecht, Carlo Knupp, Peter M. G. Munro, Eric Ezra, John M. Squire, Koji Ichihara, Hidefumi Kitazawa, Yusuke Iguchi, Tomohiko J. Itoh, Greta Pifat, Marina Kveder, Slavko Pečar, Milan Schara, Deepak Nair, Kavita Singh, Kanury V. S. Rao, Kanwaljeet Kaur, Deepti Jain, B. Sundaravadivel, Manisha Goel, D. M. Salunke, E. I. Kovalenko, G. N. Semenkova, S. N. Cherenkevich, T. Lakshmanan, D. Sriram, S. Srinivasan, D. Loganathan, T. S. Ramalingam, J. A. Lebrón, P. J. Bjorkman, A. K. Singh, T. N. Gayatri, Ernesto R. Caffarena, J. Raul Grigera, Paulo M. Bisch, V. Kiessling, P. Fromherz, K. N. Rao, S. M. Gaikwad, M. I. Khan, C. G. Suresh, P. Kaliannan, M. Elanthiraiyan, K. Chadha, J. Payne, J. L. Ambrus, M. P. N. Nair, Madhavan P. N. Nair, S. Mahajan, K. C. Chadha, R. Hewitt, S. A. Schwartz, J. Bourguignon, M. Faure, C. Cohen-Addad, M. Neuburger, R. Ober, L. Sieker, D. Macherel, R. Douce, D. S. Gurumurthy, S. Velmurugan, Z. Lobo, Ratna S. Phadke, Prashant Desai, I. M. Guseinova, S. Yu. Suleimanov, I. S. Zulfugarov, S. N. Novruzova, J. A. Aliev, M. A. Ismayilov, T. V. Savchenko, D. R. Alieva, Petr Ilík, Roman Kouřil, Hana Bartošková, Jan Nauš, Jvoti U. Gaikwad, Sarah Thomas, P. B. Vidyasagar, G. Garab, I. Simidjiev, S. Rajagopal, Zs. Várkonyi, S. Stoylova, Z. Cseh, E. Papp, L. Mustárdy, A. Holzenburg, R. Bruder, U. K. Genick, T. T. Woo, D. P. Millar, K. Gerwert, E. D. Getzoff, Tamás Jávorfí, Győző Garab, K. Razi Naqvi, Md. Kalimullah, Jyoti Gaikwad, Manoj Semwal, Roman Kouril, Petr Ilik, Man Naus, István Pomozi, Gábor Horváth, Rüdiger Wehner, Gary D. Bernard, Ana Damjanović, Thorsten Ritz, Klaus Schulten, Wang Jushuo, Shan Jixiu, Gong Yandao, Kuang Tingyun, Zhao Nanming, Arvi Freiberg, Kõu Timpmann, Rein Ruus, Neal W. Woodbury, E. V. Nemtseva, N. S. Kudryasheva, A. G. Sizykh, V. N. Shikhov, T. V. Nesterenko, A. A. Tikhomirov, Giorgio Forti, Giovanni Finazzi, Alberto Furia, Romina Paola Barbagallo, S. Iskenderova, R. Agalarov, R. Gasanov, Miyashita Osamu, G. O. Nobuhiro, R. K. Soni, M. Ramrakhiani, Hiromasa Yagi, Kacko Tozawa, Nobuaki Sekino, Tomoyuki Iwabuchi, Masasuke Yoshida, Hideo Akutsu, A. V. Avetisyan, A. D. Kaulen, V. P. Skulachev, B. A. Feniouk, Cécile Breyton, Werner Kühlbrandt, Maria Assarsson, Astrid Gräslund, G. Horváth, B. Libisch, Z. Gombos, N. V. Budagovskaya, N. Kudryasheva, Erisa Harada, Yuki Fukuoka, Tomoaki Ohmura, Arima Fukunishi, Gota Kawai, Kimitsuna Watanabe, Jure Derganc, Bojan Božič, Saša Svetina, Boštjan Žekš, J. F. Y. Hoh, Z. B. Li, G. H. Rossmanith, E. L. de Beer, B. W. Treijtel, P. L. T. M. Frederix, T. Blangè, S. Hénon, F. Galtet, V. Laurent, E. Planus, D. Isabey, L. S. Rath, P. K. Dash, M. K. Raval, C. Ramakrishnan, R. Balaram, Milan Randic, Subhash C. Basak, Marjan Vracko, Ashesh Nandy, Dragan Amic, Drago Beslo, Sonja Nikolic, Nenad Trinajstic, J. Walahaw, Marc F. J. Lensink, Boojala V. B. Reddy, Ilya N. Shindylov, Philip E. Bourne, M. C. Donnamaria, J. de Xammar Oro, J. R. Grigera, Monica Neagu, Adrian Neagu, Matej Praprotnik, Dušanka Janežič, Pekka Mark, Lennart Nilsson, L. La Fata, Laurent E. Dardenne, Araken S. Werneck, Marçal de O. Neto, N. Kannan, S. Vishveshwara, K. Veluraja, Gregory D. Grunwald, Alexandra T. Balaban, Kanika Basak, Brian D. Gute, Denise Mills, David Opitz, Krishnan Balasubramanian, G. I. Mihalas, Diana Lungeanu, G. Macovievici, Raluca Gruia, C. Cortez-Maghelly, B. Dalcin, E. P. Passos, S. Blesic, M. Ljubisavljevic, S. Milosevic, D. J. Stratimirovic, Nandita Bachhawat, Shekhar C. Mande, A. Nandy, Ayumu Saito, Koichi Nishigaki, Mohammed Naimuddin, Takatsugu Hirokawa, Mitsuo Ono, Hirotomo Takaesu, M. I. El Gohary, Abdalla S. Ahmed, A. M. Eissa, Hiroshi Nakashima, G. P. S. Raghava, N. Kurgalvuk, O. Goryn, Bernard S. Gerstman, E. V. Gritsenko, N. N. Remmel, O. M. Maznyak, V. A. Kratasyuk, E. N. Esimbekova, D. Tchitchkan, S. Koulchitsky, A. Tikhonov, A. German, Y. Pesotskaya, S. Pashkevich, S. Pletnev, V. Kulchitsky, Umamaheswar Duvvuri, Sridhar Charagundla, Rahim Rizi, John S. Leigh, Ravinder Reddy, Mahesh Kumar, O. Coshic, P. K. Julka, O. K. Rath, NR. Jagannathan, Karina Roxana Iliescu, Maria Sajin, Nicolcta Moisoi, Ileana Petcu, A. I. Kuzmenko, R. P. Morozova, I. A. Nikolenko, G. V. Donchenko, M. K. Rahman, M. M. Ahmed, Takehiro Watanabe, Y. Rubin, H. Gilboa, R. Sharony, R. Ammar, G. Uretzky, M. Khubchandani, H. N. Mallick, V. Mohan Kumar, Arijitt Borthakur, Erik M. Shapiro, M. Gulnaz Begum, Mahaveer N. Degaonkar, S. Govindasamy, Ivan Dimitrov, T. A. Kumosani, W. Bild, I. Stefanescu, G. Titescu, R. Iliescu, C. Lupusoru, V. Nastasa, I. Haulica, Gopal Khetawat, N. Faraday, M. Nealen, S. Noga, P. F. Bray, T. V. Ananieva, E. A. Lycholat, MV. Kosevich, S. G. Stepanyan, S. V. Antonyuk, R. Khachatryan, H. Arakelian, A. Kumar, S. Ayrapetyan, V. Mkheyan, S. Agadjanyan, A. Khachatryan, S. S. Rajan, V. Kabaleeswaran, Geetha Gopalakrishnan, T. R. Govindachari, Meera Ramrakhiani, Phillip Lowe, Andrew Badley, David C. Cullen, H. Hermel, W. Schmahl, H. Möhwald, Nirmalya Majumdar, Joydip Das, András Dér, Loránd Kelemen, László Oroszi, András Hámori, Jeremy J. Ramsden, Pál Ormos, D. Savitri, Chanchal K. Mitra, Toshio Yanagida, Seiji Esaki, Yuji Kimura, Tomoyuki Nishida, Yosiyuki Sowa, M. Radu, V. K. Koltover, Ya. I. Estrin, L. A. Kasumova, V. P. Bubnov, E. E. Laukhina, Rajiv Dotta, M. Degaonkar, P. Raghunathan, Rama Jayasundar, Pavel Novák, Milan Marko, Ivan Zahradník, Hiroaki Hirata, Hidetake Miyata, J. Balaji, P. Sengupta, S. Maiti, M. Gonsalves, A. L. Barker, J. V. Macpherson, D. O’Hare, C. P. Winlove, P. R. Unwin, R. Phillip, S. Banerjee, G. Ravindra Kumar, K. Nagayaka, R. Danev, S. Sugitani, K. Murata, Michael Gősch, H. Blom, P. Thyberg, Z. Földes-Papp, G. Björk, J. Holm, T. Heino, Masashi Yokochi, Fuyuhiko Inagaki, Masami Kusunoki, E. K. Matthews, J. Pines, Yu. P. Chukova, Vitaly K. Koltover, Geetanjali Bansal, Uma Singh, M. P. Bansal, Kotoko Nakata, Tastuya Nakano, Tsuguchika Kaminuma, B. P. S. Kang, U. Singh, Bonn Kirn, Neja Potocnik, Vito Stare, Latal Shukla, V. Natarajan, T. P. A. Devasagayam, M. D. Sastry, P. C. Kesavan, R. Sayfutdinov, V. V. Adamovich, D. Yu. Rogozin, A. G. Degermendzhy, C. L. Khetrapal, G. A. Nagana Gowda, Kedar Nath Ghimire, Ishida Masaru, H. Fujita, S. Ishiwata, Y. Kishimoto, S. Kawahara, M. Suzuki, H. Mori, M. Mishina, Y. Kirino, H. Ohshima, A. S. Dukhin, V. N. Shilov, P. J. Goetz, and R. K. Mishra
- Subjects
0303 health sciences ,biology ,General Medicine ,010402 general chemistry ,01 natural sciences ,Horseradish peroxidase ,General Biochemistry, Genetics and Molecular Biology ,0104 chemical sciences ,03 medical and health sciences ,Biochemistry ,Manganese porphyrin ,biology.protein ,Enzyme reconstitution ,General Agricultural and Biological Sciences ,030304 developmental biology - Published
- 1999
25. Structure and function of chromophores in R-phycoerythrin at 1.9 � resolution
- Author
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Jiping Zhang, Tao Jiang, and Dong-Cai Liang
- Subjects
Electron density ,Phycourobilin ,Resolution (electron density) ,Crystal structure ,Chromophore ,Biochemistry ,chemistry.chemical_compound ,symbols.namesake ,Crystallography ,Protein structure ,Fourier transform ,chemistry ,Structural Biology ,symbols ,Molecule ,Molecular Biology - Abstract
The crystal structure of R-Phycoerythrin (R-PE) from Polysiphonia urceolata has been refined to a resolution of 1.9 A, based on the atomic coordinates of R-PE determined at 2.8 A resolution, through the use of difference Fourier method and steorochemistry parameters restrained refinement with model adjustment according to the electron density map. Crystallographic R-factor of the refined model is 0.195 (Rfree = 0.282) from 8-1.9 A. High resolution structure of R-PE showed precise interactions between the chromophores and protein residues, which explained the spectrum characteristic and function of chromophores. Four chiral atoms of phycourobilin (PUB) were identified as C(4)-S, C(16)-S, C(21)-S, and C(20)-R. In addition to the coupling distances of 19 A to 45 A between the chromophores which were observed and involved in the energy transfer pathway, high resolution structure of R-PE suggested other pathways of energy transfer, such as the ultrashort distance between alpha140a and beta155. It has been proposed that aromatic residues in linker proteins not only influence the conformation of chromophore, but may also bridge chromophores to improve the energy transfer efficiency.
- Published
- 1999
26. Deoxyhypusine Hydroxylase from Plasmodium vivax, the Neglected Human Malaria Parasite: Molecular Cloning, Expression and Specific Inhibition by the 5-LOX Inhibitor Zileuton
- Author
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Atemnkeng, Veronika Anyigoh, Pink, Mario, Schmitz-Spanke, Simone, Wu, Xian-Jun, Dong, Liang-Liang, Zhao, Kai-Hong, May, Caroline, Laufer, Stefan, Langer, Barbara, and Kaiser, Annette
- Subjects
Drugs and Devices ,Drug Research and Development ,Transcription, Genetic ,Molecular Sequence Data ,Medizin ,lcsh:Medicine ,Gene Expression ,Pathogenesis ,Biochemistry ,Microbiology ,Mixed Function Oxygenases ,parasitic diseases ,Drug Discovery ,Parasitic Diseases ,Malaria, Vivax ,Animals ,Cluster Analysis ,Humans ,Hydroxyurea ,Plasmodium Vivax ,ddc:610 ,Amino Acid Sequence ,Lipoxygenase Inhibitors ,Parasite Evolution ,Cloning, Molecular ,lcsh:Science ,Biology ,ddc:615 ,Arachidonate 5-Lipoxygenase ,lcsh:R ,Phycocyanin ,Malaria ,Enzyme Activation ,Infectious Diseases ,Medizinische Fakultät » Universitätsklinikum Essen » Institut für Pharmakogenetik ,Medical Microbiology ,Medicine ,lcsh:Q ,Parasitology ,Sequence Alignment ,Research Article ,Biotechnology - Abstract
Primaquine, an 8-aminoquinoline, is the only drug which cures the dormant hypnozoites of persistent liver stages from P. vivax. Increasing resistance needs the discovery of alternative pathways as drug targets to develop novel drug entities. Deoxyhypusine hydroxylase (DOHH) completes hypusine biosynthesis in eukaryotic initiation factor (eIF-5A) which is the only cellular protein known to contain the unusual amino acid hypusine. Modified EIF-5A is important for proliferation of the malaria parasite. Here, we present the first successful cloning and expression of DOHH from P. vivax causing tertiary malaria. The nucleic acid sequence of 1041 bp encodes an open reading frame of 346 amino acids. Histidine tagged expression of P. vivax DOHH detected a protein of 39.01 kDa in E. coli. The DOHH protein from P. vivax shares significant amino acid identity to the simian orthologues from P. knowlesi and P. yoelii strain H. In contrast to P. falciparum only four E-Z-type HEAT-like repeats are present in P. vivax DOHH with different homology to phycocyanin lyase subunits from cyanobacteria and in proteins participating in energy metabolism of Archaea and Halobacteria. However, phycocyanin lyase activity is absent in P. vivax DOHH. The dohh gene is present as a single copy gene and transcribed throughout the whole erythrocytic cycle. Specific inhibition of recombinant P. vivax DOHH is possible by complexing the ferrous iron with zileuton, an inhibitor of mammalian 5-lipoxygenase (5-LOX). Ferrous iron in the active site of 5-LOX is coordinated by three conserved histidines and the carboxylate of isoleucine673. Zileuton inhibited the P. vivax DOHH protein with an IC50 of 12,5 nmol determined by a relative quantification by GC/MS. By contrast, the human orthologue is only less affected with an IC50 of 90 nmol suggesting a selective iron-complexing strategy for the parasitic enzyme. OA Förderung 2013
- Published
- 2013
27. RecOR complex including RecR N-N dimer and RecO monomer displays a high affinity for ssDNA
- Author
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Pu Gao, Shun Liu, Ang Gao, Xiao-Xue Yan, Xiao-Min An, Dong-Cai Liang, Qun Tang, and Yan-Ping Liu
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Models, Molecular ,Stereochemistry ,Dimer ,Lysine ,Mutant ,DNA, Single-Stranded ,Thermoanaerobacter ,Plasma protein binding ,Biology ,Hydrophobic effect ,chemistry.chemical_compound ,Monomer ,Tetramer ,chemistry ,Biochemistry ,Bacterial Proteins ,Structural Biology ,Genetics ,Binding site ,Protein Multimerization ,Dimerization ,DNA ,Protein Binding - Abstract
RecR is an important recombination mediator protein in the RecFOR pathway. RecR together with RecO and RecF facilitates RecA nucleoprotein filament formation and homologous pairing. Structural and biochemical studies of Thermoanaerobacter tengcongensis RecR (TTERecR) and its series mutants revealed that TTERecR uses the N-N dimer as a basic functional unit to interact with TTERecO monomer. Two TTERecR N-N dimers form a ring-shaped tetramer via an interaction between their C-terminal regions. The tetramer is a result of crystallization only. Hydrophobic interactions between the entire helix-hairpin-helix domains within the N-terminal regions of two TTERecR monomers are necessary for formation of a RecR functional N-N dimer. The TTERecR N-N dimer conformation also affects formation of a hydrophobic patch, which creates a binding site for TTERecO in the TTERecR Toprim domain. In addition, we demonstrate that TTERecR does not bind single-stranded DNA (ssDNA) and binds double-stranded DNA very weakly, whereas TTERecOR complex can stably bind DNA, with a higher affinity for ssDNA than double-stranded DNA. Based on these results, we propose an interaction model for the RecOR:ssDNA complex.
- Published
- 2012
28. High-resolution structures of AidH complexes provide insights into a novel catalytic mechanism for N-acyl homoserine lactonase
- Author
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Ang Gao, Xiao Xue Yan, Gui Ying Mei, Qun Tang, Shun Liu, Xiao Min An, Hui Wen, Li-Qun Zhang, Ping Wang, Yan Ping Liu, and Dong Cai Liang
- Subjects
Cell signaling ,Stereochemistry ,Homoserine ,Virulence ,Cell Communication ,Ochrobactrum ,medicine.disease_cause ,α/β-hydrolases ,Catalysis ,Enzyme catalysis ,Substrate Specificity ,chemistry.chemical_compound ,Structural Biology ,Catalytic Domain ,Hydrolase ,medicine ,covalent catalysis ,lactonases ,biology ,acid–base catalysis ,Hydrolysis ,food and beverages ,Active site ,quorum sensing ,Pathogenic bacteria ,General Medicine ,biochemical phenomena, metabolism, and nutrition ,Hydrogen-Ion Concentration ,Research Papers ,Quorum sensing ,chemistry ,Biochemistry ,biology.protein ,Mutagenesis, Site-Directed ,Carboxylic Ester Hydrolases - Abstract
Crystal structures of the AHL-lactonase AidH in complex with substrate and product are reported at high resolution and a catalytic mechanism is proposed for the metal-independent AHL-lactonase., Many pathogenic bacteria that infect humans, animals and plants rely on a quorum-sensing (QS) system to produce virulence factors. N-Acyl homoserine lactones (AHLs) are the best-characterized cell–cell communication signals in QS. The concentration of AHL plays a key role in regulating the virulence-gene expression and essential biological functions of pathogenic bacteria. N-Acyl homoserine lactonases (AHL-lactonases) have important functions in decreasing pathogenicity by degrading AHLs. Here, structures of the AHL-lactonase from Ochrobactrum sp. (AidH) in complex with N-hexanoyl homoserine lactone, N-hexanoyl homoserine and N-butanoyl homoserine are reported. The high-resolution structures together with biochemical analyses reveal convincing details of AHL degradation. No metal ion is bound in the active site, which is different from other AHL-lactonases, which have a dual Lewis acid catalysis mechanism. AidH contains a substrate-binding tunnel between the core domain and the cap domain. The conformation of the tunnel entrance varies with the AHL acyl-chain length, which contributes to the binding promiscuity of AHL molecules in the active site. It also supports the biochemical result that AidH is a broad catalytic spectrum AHL-lactonase. Taken together, the present results reveal the catalytic mechanism of the metal-independent AHL-lactonase, which is a typical acid–base covalent catalysis.
- Published
- 2012
29. Crystallization and preliminary crystallographic studies of pyridoxal kinase from sheep brain
- Author
-
Chi Kong Lau, Sheng Quan Liu, Tao Jiang, Wenrui Chang, Jiping Zhang, Yun Chung Leung, Minghui Li, Francis Kwok, Dong Cai Liang, and Xiao Min An
- Subjects
chemistry.chemical_classification ,Sheep ,biology ,Protein Conformation ,Stereochemistry ,Brain ,General Medicine ,Metabolism ,Crystallography, X-Ray ,Phosphate ,Pyridoxal kinase ,Cofactor ,Amino acid ,Crystallography ,chemistry.chemical_compound ,Enzyme ,chemistry ,Biochemistry ,Structural Biology ,Sodium citrate ,biology.protein ,Animals ,Crystallization ,Pyridoxal - Abstract
Pyridoxal kinase (ATP:pyridoxal 5'-phosphotransferase; EC 2.7.1.35) is a key enzyme in the transformation of vitamin B(6) to pyridoxal-5'-phosphate. Pyridoxal-5'-phosphate is the crucial cofactor required by numerous enzymes involved in the metabolism of amino acids and the synthesis of many neurotransmitters. Pyridoxal kinase from sheep brain was crystallized in an orthorhombic form using the hanging-drop vapour-diffusion method with sodium citrate as the precipitant. The crystals belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 59.8, b = 94.4, c = 128.2 A, and diffract to a resolution of 2.1 A. Crystals were transferred into a soaking liquid without citrate and two heavy-atom derivatives were prepared.
- Published
- 2002
30. Crystallization and preliminary crystallographic analysis of manganese superoxide dismutase from Bacillus halodenitrificans
- Author
-
Tschining Chang, Ming-Yih Liu, Dong-Cai Liang, Jiping Zhang, Mei Li, Jun Liao, Jean Le Gall, Wenrui Chang, and Lulu Gui
- Subjects
chemistry.chemical_classification ,biology ,Protein Conformation ,Superoxide Dismutase ,Biophysics ,Bacillus ,Cell Biology ,Crystallography, X-Ray ,Biochemistry ,Manganese Superoxide Dismutase ,Halophile ,Catalysis ,law.invention ,Superoxide dismutase ,Crystallography ,chemistry.chemical_compound ,Enzyme ,Monomer ,chemistry ,law ,biology.protein ,Crystallization ,Molecular Biology ,Bacillus halodenitrificans - Abstract
Manganese superoxide dismutase (GP-MnSOD), a component of the so-called `green protein' (green protein complex) from the facultative anaerobic halodenitrifier Bacillus halodenitrificans , has been crystallized using the hanging-drop vapor diffusion method. Crystals have unit-cell parameters a = b =93.4 A, c =65.0 A, and belong to the space group P4 3 2 1 2. Preliminary analysis indicates there is one monomer in each asymmetric unit. The structural information from this enzyme will enrich our knowledge on its high catalytic activity and its possible role in green protein complex.
- Published
- 2002
31. Serum decoy receptor 3, a potential new biomarker for sepsis
- Author
-
Jinsheng Hong, Sunghee Kim, Dong-Yu Liang, Lurong Zhang, Xiaoli Lou, Yanqiang Hou, Shanmin Yang, Zhenhuan Zhang, Liang Peng, Mei Zhang, Deping Han, and Ping Xu
- Subjects
Male ,Clinical Biochemistry ,Enzyme-Linked Immunosorbent Assay ,Biochemistry ,Sepsis ,medicine ,Humans ,Blood culture ,APACHE ,Aged ,medicine.diagnostic_test ,business.industry ,Biochemistry (medical) ,Receptors, Tumor Necrosis Factor, Member 6b ,Case-control study ,General Medicine ,Middle Aged ,medicine.disease ,Systemic inflammatory response syndrome ,ROC Curve ,Shock (circulatory) ,Case-Control Studies ,Immunology ,Biomarker (medicine) ,Tumor necrosis factor alpha ,Female ,Decoy receptor 3 ,medicine.symptom ,business ,Biomarkers - Abstract
Sepsis, a common deadly systemic infection caused by a variety of pathogens, has some clinical symptoms similar to the systemic inflammatory response syndrome (SIRS), a whole-body non-infectious inflammatory reaction to severe insults, such as burn, trauma, hypotensive shock and so on. Treatment of sepsis depends mainly on anti-microbial, while remedy for SIRS might require steroids that could possibly enhance the spread of microbes. Unfortunately, it is very difficult to distinguish these two completely different serious conditions without blood culture, which takes days to grow and identify causative pathogens. We examined a biomarker, serum decoy receptor 3 (DcR3), was evaluated for its utility in the differential diagnosis between sepsis and SIRS.Serum DcR3 level in 118 healthy controls, 24 sepsis patients and 43 SIRS patients, was quantitatively measured by enzyme-linked immunosorbent assay (ELISA).The serum DcR3 was significantly increased in sepsis patients compared with SIRS patients and healthy controls (6.11±2.58 ng/ml vs 2.62±1.46 ng/ml, and 0.91±0.56 ng/ml, respectively, p0.001). The areas under the receiver operating characteristic curve of DcR3 for the normal vs. SIRS, normal vs. sepsis and SIRS vs. sepsis were 0.910 (0.870-0.950), 0.992 (0.984-1.000) and 0.896 (0.820-0.973), respectively. In addition, the DcR3 exhibited a positive correlation coefficient with APACHE II score, a most commonly used index for the severity of sepsis (r=0.556, p=0.005).The serum DcR3 has a potential to serve as a new biomarker for sepsis with its high specificity and sensitivity.
- Published
- 2011
32. Structure of HsdS Subunit from Thermoanaerobacter tengcongensis Sheds Lights on Mechanism of Dynamic Opening and Closing of Type I Methyltransferase
- Author
-
Xiao-Min An, Xiao-Xue Yan, Qun Tang, Pu Gao, and Dong-Cai Liang
- Subjects
Macromolecular Assemblies ,DNA, Bacterial ,Models, Molecular ,Methyltransferase ,Stereochemistry ,Protein Conformation ,Protein subunit ,Biophysics ,lcsh:Medicine ,Thermoanaerobacter ,Biology ,Crystallography, X-Ray ,DNA Restriction-Modification Enzymes ,Biochemistry ,chemistry.chemical_compound ,Protein structure ,Bacterial Proteins ,Transferases ,DNA-binding proteins ,Electrophoretic mobility shift assay ,lcsh:Science ,Protein chemistry ,Multidisciplinary ,Enzyme Classes ,lcsh:R ,Proteins ,DNA ,Genomics ,Methyltransferases ,biology.organism_classification ,Enzyme structure ,Enzymes ,body regions ,Nucleic acids ,Protein Subunits ,chemistry ,Enzyme Structure ,Mutation ,lcsh:Q ,Structural Genomics ,DNA modification ,Research Article ,Protein Binding - Abstract
Type I DNA methyltransferases contain one specificity subunit (HsdS) and two modification subunits (HsdM). The electron microscopy model of M.EcoKI-M2S1 methyltransferase shows a reasonable closed state of this clamp-like enzyme, but the structure of the open state is still unclear. The 1.95 A crystal structure of the specificity subunit from Thermoanaerobacter tengcongensis (TTE-HsdS) shows an unreported open form inter-domain orientation of this subunit. Based on the crystal structure of TTE-HsdS and the closed state model of M.EcoKI-M2S1, we constructed a potential open state model of type I methyltransferase. Mutational studies indicated that two α-helices (aa30-59 and aa466-495) of the TTE-HsdM subunit are important inter-subunit interaction sites in the TTE-M2S1 complex. DNA binding assays also highlighted the importance of the C-terminal region of TTE-HsdM for DNA binding by the TTE-M2S1 complex. On the basis of structural analysis, biochemical experiments and previous studies, we propose a dynamic opening and closing mechanism for type I methyltransferase.
- Published
- 2011
33. Crystal structure of a putative methylmalonyl-coenzyme A epimerase from Thermoanaerobacter tengcongensis at 2.0 A resolution
- Author
-
Xiao-Xue Yan, Dong-Cai Liang, Pu Gao, and Liang Shi
- Subjects
Models, Molecular ,Protein Conformation ,Glyoxylate cycle ,Racemases and Epimerases ,Thermoanaerobacter ,Isomerase ,Crystallography, X-Ray ,Biochemistry ,chemistry.chemical_compound ,Lactoylglutathione lyase ,Mutase ,Protein structure ,Biosynthesis ,Bacterial Proteins ,Structural Biology ,Catalytic Domain ,Protein Structure, Quaternary ,Molecular Biology ,chemistry.chemical_classification ,biology ,Cobalt ,biology.organism_classification ,Recombinant Proteins ,Amino acid ,chemistry ,biology.protein ,Dimerization - Abstract
Methylmalonyl-CoA is an important metabolic intermediate that exists in several key degradative and biosynthetic pathways.1 The pathway responsible for the degradation of branched amino acids and odd chain fatty acids involves three steps. In the first step, a biotindependent carboxylation produces the S-epimer of methylmalonyl-CoA. The third step, the B12-dependent methylmalonyl-CoA mutase converts the R-epimer of methylmalonyl-CoA to succinyl-CoA.1 This key epimerization between the two steps is carried out by the essential enzyme methylmalonyl-CoA epimerase (MMCE: EC number 5.1.99.1), which catalyzes the conversion of (2S)methylmalonyl-CoA to (2R)-methylmalonyl-CoA. In prokaryotes, MMCE participated in autotrophic CO2 fixation via the 3-hydroxypropionate pathway, in propionate fermentation, the regeneration of glyoxylate and in the biosynthesis of polyketide antibiotics.2–6 In animals, defects of this pathway can result in a buildup of methylmalonic acid, which causes severe acidosis and also damages the central nervous system.7,8 In this study, we determined the crystal structure of TTE0360 from Thermoanaerobacter tengcongensis to 2.0 A resolution using single-wavelength anomalous dispersion (SAD) by short cryo-soaking with a high concentration of potassium iodide.9,10 In GenBank database, the gene tte0360 is predicted to be glyoxalase I, a member of glyoxalase superfamily. However, the TTE0360 structure is very different than the released structures of glyoxalase I. A search for the 3D homologs using DALI11 shows that TTE0360 has significant structural similarity with the MMCE from Propionibacterium shermanii,12 which is also a member of glyoxalase superfamily. The fold type of the TTE0360 molecule belongs to the vicinal-oxygen-chelate superfamily (VOC).13 The similarities of structure folds, dimer formation, and active sites between TTE0360 and MMCE, suggest that the protein TTE0360 may be the MMCE from T. tengcongensis.
- Published
- 2009
34. Determination of berberine inRhizoma coptidis and its preparations by non-aqueous capillary electrophoresis
- Author
-
Song-gang Ji, Dong-sheng Liang, Zi-ming Xu, Yutian Wu, Yifeng Chai, and Guo-qing Zhang
- Subjects
Pharmacology ,Aqueous solution ,Chromatography ,Clinical Biochemistry ,General Medicine ,Buffer solution ,Biochemistry ,Analytical Chemistry ,chemistry.chemical_compound ,Electrophoresis ,Acetic acid ,Capillary electrophoresis ,Berberine ,chemistry ,Drug Discovery ,Methanol ,Molecular Biology ,Sodium acetate - Abstract
A non-aqueous capillary electrophoretic method was established for the determination of berberine in Rhizoma coptidis and its preparations. The effects of organic solvent and the concentrations of sodium acetate were studied, which showed that berberine in extracts of traditional Chinese medicine can be separated successfully in a buffer solution of 75 mmol/L of sodium acetate in methanol containing 1 mol/L of acetic acid. The simple and rapid method was linear in the range 25-200 microgram/mL of berberine and had a good reproducibility, with the relative standard deviation below 2%. Non-aqueous capillary electrophoresis is a satisfactory system for the analysis of alkaloids in traditional Chinese medicine.
- Published
- 1999
35. Determination of tetrahydropalmatine in Chinese traditional medicine by nonaqueous capillary electrophoresis
- Author
-
Yutian Wu, Song-gang Ji, Guo-qing Zhang, Xueping Yin, Yifeng Chai, Dong-sheng Liang, and Zi-ming Xu
- Subjects
Chromatography ,biology ,Clinical Biochemistry ,Buffer solution ,Corydalis ,biology.organism_classification ,Tetrahydropalmatine ,Biochemistry ,Analytical Chemistry ,chemistry.chemical_compound ,Acetic acid ,Capillary electrophoresis ,chemistry ,Methanol ,Sodium acetate ,Chinese traditional medicine - Abstract
Tetrahydropalmatine in Rhizoma corydalis and its preparations were separated and determined with no pretreatment in the buffer solution of 50 mmol/L of sodium acetate in methanol containing 2 mol/L acetic acid.
- Published
- 1999
36. Crystal structure of human dynein light chain Dnlc2A: structural insights into the interaction with IC74
- Author
-
Dong-Cai Liang, Qun Tang, Jun-Feng Liu, Lu-Lu Gui, Xiao-Min An, Zhan-Xin Wang, and Xin-Quan Wang
- Subjects
Models, Molecular ,Binding Sites ,Chemistry ,Hydrogen bond ,Dynein ,Biophysics ,Dyneins ,Cell Biology ,Immunoglobulin light chain ,Crystallography, X-Ray ,Biochemistry ,Transport protein ,Protein Structure, Tertiary ,Motor protein ,Residue (chemistry) ,Crystallography ,Structural Homology, Protein ,Helix ,Molecule ,Humans ,Protein Structure, Quaternary ,Molecular Biology ,Dimerization ,Protein Binding - Abstract
The human light chain of the motor protein dynein, Dnlc2A, is also a novel TGF-beta-signaling component, which is altered with high frequency in epithelial ovarian cancer. It is an important mediator of dynein and the development of cancer, owing to its ability to bind to the dynein intermediate light chain (DIC) IC74 and to regulate TGF-beta-dependent transcriptional events. Here we report the 2.1-A crystal structure of Dnlc2A using single anomalous diffraction. The proteins form a homodimer in solution and interact mainly through the helix alpha(2), strand beta(3), and the loop following this strand in each protein to generate a 10-stranded beta-sheet core. The surface of the beta-sheet core is mainly positively charged and predicted (by software PPI-Pred) to be the site that interacts with other partners. At the same time, the residues 79-82, 88, and 90 of each molecule formed two holes in the core. Residue 89 of each molecule, which is crucial for the DIC binding function of Dnlc2A, is within the holes. On the basis of these observations, we propose that the homodimer is the structural and functional unit maintained by hydrogen bonding interactions and hydrophobic packing, and that the patch of the surface of the beta-sheet core is the main area of interaction with other partners. Furthermore, the two holes would be the key sites to interact with IC74.
- Published
- 2006
37. Crystal structure of pyridoxal kinase in complex with roscovitine and derivatives
- Author
-
Hervé Galons, Dong-Cai Liang, Laurent Meijer, Yongqin Wan, Lin Tang, Wenrui Chang, Stéphane Bach, Minghui Li, Feng Wang, Nathanael S. Gray, Yoan Ferandin, Jens Reinhardt, Peng Cao, and Tao Jiang
- Subjects
Models, Molecular ,Stereochemistry ,Macromolecular Substances ,Swine ,Crystallography, X-Ray ,Ligands ,Biochemistry ,Cofactor ,chemistry.chemical_compound ,Cyclin-dependent kinase ,Roscovitine ,Transferase ,Animals ,Binding site ,Pyridoxal Kinase ,Molecular Biology ,Pyridoxal ,Nuclear Magnetic Resonance, Biomolecular ,Protein Kinase Inhibitors ,Binding Sites ,biology ,Molecular Structure ,Kinase ,Cell Biology ,Pyridoxal kinase ,Protein Structure, Tertiary ,chemistry ,Purines ,biology.protein ,Pyridoxamine - Abstract
Pyridoxal kinase (PDXK) catalyzes the phosphorylation of pyridoxal, pyridoxamine, and pyridoxine in the presence of ATP and Zn2+. This constitutes an essential step in the synthesis of pyridoxal 5′-phosphate (PLP), the active form of vitamin B6, a cofactor for over 140 enzymes. (R)-Roscovitine (CYC202, Seliciclib) is a relatively selective inhibitor of cyclin-dependent kinases (CDKs), currently evaluated for the treatment of cancers, neurodegenerative disorders, renal diseases, and several viral infections. Affinity chromatography investigations have shown that (R)-roscovitine also interacts with PDXK. To understand this interaction, we determined the crystal structure of PDXK in complex with (R)-roscovitine, N6-methyl-(R)-roscovitine, and O6-(R)-roscovitine, the two latter derivatives being designed to bind to PDXK but not to CDKs. Structural analysis revealed that these three roscovitines bind similarly in the pyridoxal-binding site of PDXK rather than in the anticipated ATP-binding site. The pyridoxal pocket has thus an unexpected ability to accommodate molecules different from and larger than pyridoxal. This work provides detailed structural information on the interactions between PDXK and roscovitine and analogs. It could also aid in the design of roscovitine derivatives displaying strict selectivity for either PDXK or CDKs.
- Published
- 2005
38. 1.88 A crystal structure of the C domain of hCyP33: a novel domain of peptidyl-prolyl cis-trans isomerase
- Author
-
Cai-Hong Yun, Tao Wang, Wenrui Chang, Dong-Cai Liang, and Shenyan Gu
- Subjects
Models, Molecular ,biology ,Protein family ,Protein Conformation ,Biophysics ,Active site ,Cypa ,Cell Biology ,Isomerase ,biology.organism_classification ,Crystallography, X-Ray ,Biochemistry ,Cyclophilin A ,Cyclophilins ,Cyclic nucleotide-binding domain ,Cyclosporin a ,biology.protein ,Molecular Biology ,Cyclophilin - Abstract
Cyclophilins (CyPs) are a widespreading protein family in living organisms and possess the activity of peptidyl-prolyl cis–trans isomerase (PPIase), which is inhibited by cyclosporin A (CsA). The human nuclear cyclophilin (hCyP33) is the first protein which was found to contain two RNA binding domains at the amino-terminus and a PPIase domain at the carboxyl-terminus. We isolated the hCyP33 gene from the human hematopoietic stem/progenitor cells and expressed it in Escherichia coli, and determined the crystal structure of the C domain of hCyP33 at 1.88 A resolution. The core structure is a β-barrel covered by two α-helices. Superposition of the structure of the C domain of hCyP33 with the structure of CypA suggests that the C domain contains PPIase active site which binds to CsA. Furthermore, C domain seems to be able to bind with the Gag-encoded capsid (CA) of HIV-1 and may affect the viral replication of HIV-1. A key residue of the active site is changed from Ala-103-CypA to Ser-239-hCyP33, which may affect the PPIase domain/substrates interactions.
- Published
- 2005
39. Conformational changes in the reaction of pyridoxal kinase
- Author
-
Wenrui Chang, Minghui Li, Tao Jiang, Sheng Quan Liu, Samuel Chun-Lap Lo, Dong-Cai Liang, Jiping Zhang, and Francis Kwok
- Subjects
Models, Molecular ,Stereochemistry ,Protein Conformation ,Electrons ,Plasma protein binding ,Crystallography, X-Ray ,Biochemistry ,Catalysis ,Phosphates ,chemistry.chemical_compound ,Protein structure ,Adenosine Triphosphate ,Transferase ,Animals ,Binding site ,Pyridoxal Kinase ,Molecular Biology ,chemistry.chemical_classification ,Binding Sites ,Sheep ,biology ,Chemistry ,Active site ,Brain ,Hydrogen Bonding ,Cell Biology ,Pyridoxal kinase ,Adenosine Monophosphate ,Adenosine Diphosphate ,Enzyme ,biology.protein ,Pyridoxamine ,Protein Binding - Abstract
To understand the processes involved in the catalytic mechanism of pyridoxal kinase (PLK),1 we determined the crystal structures of PLK.AMP-PCP-pyridoxamine, PLK.ADP.PLP, and PLK.ADP complexes. Comparisons of these structures have revealed that PLK exhibits different conformations during its catalytic process. After the binding of AMP-PCP (an analogue that replaced ATP) and pyridoxamine to PLK, this enzyme retains a conformation similar to that of the PLK.ATP complex. The distance between the reacting groups of the two substrates is 5.8 A apart, indicating that the position of ATP is not favorable to spontaneous transfer of its phosphate group. However, the structure of PLK.ADP.PLP complex exhibited significant changes in both the conformation of the enzyme and the location of the ligands at the active site. Therefore, it appears that after binding of both substrates, the enzyme-substrate complex requires changes in the protein structure to enable the transfer of the phosphate group from ATP to vitamin B(6). Furthermore, a conformation of the enzyme-substrate complex before the transition state of the enzymatic reaction was also hypothesized.
- Published
- 2004
40. Crystal structure of a NO-forming nitrite reductase mutant: an analog of a transition state in enzymatic reaction
- Author
-
Jean LeGall, Sheng Quan Liu, Ming Yih Liu, Wen Chang Chang, Dong Cai Liang, Jiping Zhang, Tschining Chang, and Wenrui Chang
- Subjects
Models, Molecular ,Nitrite Reductases ,Stereochemistry ,Protein Conformation ,Mutant ,Biophysics ,chemistry.chemical_element ,Crystallography, X-Ray ,Nitric Oxide ,Biochemistry ,Protein Structure, Secondary ,chemistry.chemical_compound ,Oxidoreductase ,Imidazole ,Histidine ,Alcaligenes ,Nitrite ,Site-directed mutagenesis ,Molecular Biology ,chemistry.chemical_classification ,biology ,Chemistry ,Electron Spin Resonance Spectroscopy ,Cell Biology ,Hydrogen-Ion Concentration ,Nitrite reductase ,Copper ,Enzyme assay ,Oxygen ,Mutation ,biology.protein ,Mutagenesis, Site-Directed ,Protein Binding - Abstract
I257E was obtained by site directed mutagenesis of nitrite reductase from Achromobacter cycloclastes . The mutant has no enzyme activity. Its crystal structure determined at 1.65 A resolution shows that the side-chain carboxyl group of the mutated residue, Glu257, coordinates with the type 2 copper in the mutant and blocks the contact between the type 2 copper and its solvent channel, indicating that the accessibility of the type 2 copper is essential for maintaining the activity of nitrite reductase. The carboxylate is an analog of the substrate, nitrite, but the distances between the type 2 copper and the two oxygen atoms of the side-chain carboxyl group are reversed in comparison to the binding of nitrite to the native enzyme. In the mutant, both the type 2 copper and the Ne atom on the imidazole ring of its coordinated residue His135 move in the substrate binding direction relative to the native enzyme. In addition, an EPR study showed that the type 2 copper in the mutant is in a reduced state. We propose that mutant I257E is in a state corresponding to a transition state in the enzymatic reaction.
- Published
- 2003
41. Crystal structure of earthworm fibrinolytic enzyme component a: revealing the structural determinants of its dual fibrinolytic activity
- Author
-
Jiping Zhang, Yong Tang, Lulu Gui, Wenrui Chang, Tao Jiang, and Dong-Cai Liang
- Subjects
Models, Molecular ,Proteases ,Molecular Sequence Data ,Static Electricity ,Beta sheet ,Crystallography, X-Ray ,Protein Structure, Secondary ,Substrate Specificity ,Serine ,Protein structure ,Structural Biology ,Hydrolase ,Endopeptidases ,Animals ,Amino Acid Sequence ,Binding site ,Oligochaeta ,Molecular Biology ,Serine protease ,chemistry.chemical_classification ,Binding Sites ,biology ,Chemistry ,Fibrinolysis ,Enzyme ,Biochemistry ,biology.protein ,Hydrophobic and Hydrophilic Interactions ,Sequence Alignment - Abstract
Earthworm fibrinolytic enzyme component A (EFEa) from Eisenia fetida is a strong fibrinolytic enzyme that not only directly degrades fibrin, but also activates plasminogen. Proteolytic assays further revealed that it cleaved behind various P1 residue types. The crystal structure of EFEa was determined using the MIR method and refined to 2.3A resolution. The enzyme, showing the overall polypeptide fold of chymotrypsin-like serine proteases, possesses essential S1 specificity determinants characteristic of elastase. However, the beta strand at the west rim of the S1 specificity pocket is significantly elongated by a unique four-residue insertion (Ser-Ser-Gly-Leu) after Val217, which not only provides additional substrate hydrogen binding sites for distal P residues, but also causes extension of the S1 pocket at the south rim. The S2 subsite of the enzyme was partially occluded by the bulky side-chain of residue Tyr99. Structure-based inhibitor modeling demonstrated that EFEa's S1 specificity pocket was preferable for elastase-specific small hydrophobic P1 residues, while its accommodation of long and/or bulky P1 residues was also feasible if enhanced binding of the substrate and induced fit of the S1 pocket were achieved. EFEa is thereby endowed with relatively broad substrate specificity, including the dual fibrinolysis. The presence of Tyr99 at the S2 subsite indicates a preference for P2-Gly, while an induced fit of Tyr99 was also suggested for accommodation of bigger P2 residues. This structure is the first reported for an earthworm fibrinolytic enzyme component and serine protease originating from annelid worms.
- Published
- 2002
42. Determination of icariin in Chinese traditional medicine by capillary zone electrophoresis
- Author
-
Xueping Yin, Guo-qing Zhang, Song-gang Ji, Yutian Wu, Dong-sheng Liang, Yifeng Chai, and Zi-ming Xu
- Subjects
Pharmacology ,Flavonoids ,Chromatography ,Plants, Medicinal ,Clinical Biochemistry ,Electrophoresis, Capillary ,General Medicine ,Biochemistry ,Analytical Chemistry ,chemistry.chemical_compound ,Capillary electrophoresis ,chemistry ,Drug Discovery ,Indicators and Reagents ,Acetonitrile ,Molecular Biology ,Icariin ,Chinese traditional medicine ,Chromatography, Micellar Electrokinetic Capillary ,Drugs, Chinese Herbal - Abstract
Icariin in Chinese traditional medicine was determined by an accurate and simple capillary zone electrophoresis method which used 30 mmol/L of borate solution containing 10% of acetonitrile as running buffer and needed no pretreatment. Copyright © 1999 John Wiley & Sons, Ltd.
- Published
- 1999
43. Crystal structure of allophycocyanin from red algae Porphyra yezoensis at 2.2-A resolution
- Author
-
Tao Jiang, Jiping Zhang, Dong-Cai Liang, and Jin-Yu Liu
- Subjects
Models, Molecular ,Stereochemistry ,Molecular Sequence Data ,Light-Harvesting Protein Complexes ,Trimer ,Crystal structure ,Random hexamer ,Crystallography, X-Ray ,Biochemistry ,chemistry.chemical_compound ,Phycocyanobilin ,Bacterial Proteins ,Species Specificity ,Phycobilins ,Consensus Sequence ,Molecular replacement ,Computer Simulation ,Pyrroles ,Amino Acid Sequence ,Molecular Biology ,Plant Proteins ,Sequence Homology, Amino Acid ,Hydrogen bond ,Phycocyanin ,Reproducibility of Results ,Cell Biology ,Bond length ,Crystallography ,Monomer ,chemistry ,Energy Transfer ,Tetrapyrroles ,Rhodophyta - Abstract
The crystal structure of allophycocyanin from red algae Porphyra yezoensis (APC-PY) at 2.2-A resolution has been determined by the molecular replacement method. The crystal belongs to space group R32 with cell parameters a = b = 105.3 A, c = 189.4 A, alpha = beta = 90 degrees, gamma = 120 degrees. After several cycles of refinement using program X-PLOR and model building based on the electron density map, the crystallographic R-factor converged to 19.3% (R-free factor is 26.9%) in the range of 10.0 to 2.2 A. The r.m.s. deviations of bond length and angles are 0.015 A and 2.9 degrees, respectively. In the crystal, two APC-PY trimers associate face to face into a hexamer. The assembly of two trimers within the hexamer is similar to that of C-phycocyanin (C-PC) and R-phycoerythrin (R-PE) hexamers, but the assembly tightness of the two trimers to the hexamer is not so high as that in C-PC and R-PE hexamers. The chromophore-protein interactions and possible pathway of energy transfer were discussed. Phycocyanobilin 1alpha84 of APC-PY forms 5 hydrogen bonds with 3 residues in subunit 2beta of another monomer. In R-PE and C-PC, chromophore 1alpha84 only forms 1 hydrogen bond with 2beta77 residue in subunit 2beta. This result may support and explain great spectrum difference exists between APC trimer and monomer.
- Published
- 1999
44. A proposed interaction model of the insulin molecule with its receptor
- Author
-
Zhu li Wan, Wen rui Chang, and Dong cai Liang
- Subjects
Chemical Phenomena ,Protein Conformation ,medicine.medical_treatment ,Receptor molecule ,Molecular Sequence Data ,Biophysics ,Biochemistry ,Models, Biological ,Protein Structure, Secondary ,Structure-Activity Relationship ,X-Ray Diffraction ,Amphiphile ,medicine ,Molecule ,Animals ,Insulin ,Amino Acid Sequence ,Receptor ,Chemistry ,Chemistry, Physical ,Organic Chemistry ,Interaction model ,Receptor, Insulin ,Crystallography ,Models, Chemical - Abstract
Based on the extensive structural comparisons among the determined structures of the different species and crystal forms of insulin and its derivatives in our laboratory, it was suggested that the binding interaction with the receptor molecule should take place mainly on an amphipathic surface of the insulin molecule. In the middle of this amphipathis surface, there was a hydrophobic surface with an area of about 150 A 2 , while the polar and charged groups distributing around the hydrophobic surface constructed a hydrophilic zone. The hydrophobic surface was usually covered by the extended B-chain C-terminal peptides with great mobility. The angle between the proposed binding interaction surface and the surface of dimerization was about 20°. The results from studies on structures of A1-( l -Trp) insulin and A1-( d -Trp) insulin confirmed the interaction mechanism model we proposed.
- Published
- 1994
45. Deoxyhypusine Hydroxylase from Plasmodium vivax, the Neglected Human Malaria Parasite: Molecular Cloning, Expression and Specific Inhibition by the 5-LOX Inhibitor Zileuton.
- Author
-
Atemnkeng, Veronika Anyigoh, Pink, Mario, Schmitz-Spanke, Simone, Wu, Xian-Jun, Dong, Liang-Liang, Zhao, Kai-Hong, May, Caroline, Laufer, Stefan, Langer, Barbara, and Kaiser, Annette
- Subjects
HYDROXYLASES ,PLASMODIUM vivax ,PLASMODIUM ,MOLECULAR cloning ,GENE expression ,LIPOXYGENASES ,PRIMAQUINE ,TARGETED drug delivery ,BIOTECHNOLOGY ,MICROBIOLOGY - Abstract
Primaquine, an 8-aminoquinoline, is the only drug which cures the dormant hypnozoites of persistent liver stages from P. vivax. Increasing resistance needs the discovery of alternative pathways as drug targets to develop novel drug entities. Deoxyhypusine hydroxylase (DOHH) completes hypusine biosynthesis in eukaryotic initiation factor (eIF-5A) which is the only cellular protein known to contain the unusual amino acid hypusine. Modified EIF-5A is important for proliferation of the malaria parasite. Here, we present the first successful cloning and expression of DOHH from P. vivax causing tertiary malaria. The nucleic acid sequence of 1041 bp encodes an open reading frame of 346 amino acids. Histidine tagged expression of P. vivax DOHH detected a protein of 39.01 kDa in E. coli. The DOHH protein from P. vivax shares significant amino acid identity to the simian orthologues from P. knowlesi and P. yoelii strain H. In contrast to P. falciparum only four E-Z-type HEAT-like repeats are present in P. vivax DOHH with different homology to phycocyanin lyase subunits from cyanobacteria and in proteins participating in energy metabolism of Archaea and Halobacteria. However, phycocyanin lyase activity is absent in P. vivax DOHH. The dohh gene is present as a single copy gene and transcribed throughout the whole erythrocytic cycle. Specific inhibition of recombinant P. vivax DOHH is possible by complexing the ferrous iron with zileuton, an inhibitor of mammalian 5-lipoxygenase (5-LOX). Ferrous iron in the active site of 5-LOX is coordinated by three conserved histidines and the carboxylate of isoleucine
673 . Zileuton inhibited the P. vivax DOHH protein with an IC50 of 12,5 nmol determined by a relative quantification by GC/MS. By contrast, the human orthologue is only less affected with an IC50 of 90 nmol suggesting a selective iron-complexing strategy for the parasitic enzyme. [ABSTRACT FROM AUTHOR]- Published
- 2013
- Full Text
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46. Synthesis and preliminary biological evaluation of novel pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives as potential agents against A549 lung cancer cells
- Author
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Zhang, Jin-Hua, Fan, Chuan-Dong, Zhao, Bao-Xiang, Shin, Dong-Soo, Dong, Wen-Liang, Xie, Yong-Sheng, and Miao, Jun-Ying
- Subjects
- *
LUNG cancer , *PYRAZOLONES , *ORGANIC synthesis , *REGULATION of cell growth , *STRUCTURE-activity relationship in pharmacology , *BIOCHEMISTRY , *CELLULAR pathology - Abstract
Abstract: A series of novel pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives were synthesized by the reaction of ethyl 3-aryl-1-(2-bromoethyl)-1H-pyrazole-5-carboxylate and amine in the general heating condition and microwave-assisted condition. The structures of the compounds were determined by IR, 1H NMR and mass spectroscopy, in addition, representative single-crystal structures were characterized by using X-ray diffraction analysis. Preliminary biological evaluation showed that the compounds could inhibit the growth of A549 cells in dosage- and time-dependent manners. The study on structure-activity relationships showed that compounds with 4-chlorophenyl group at pyrazole moiety, such as 5-benzyl-2-(4-chlorophenyl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one (3o) had much more inhibitory effects. Compound 3o was the most effective small molecule in inhibiting A549 cell growth and might perform its action through modulating autophagy. [Copyright &y& Elsevier]
- Published
- 2008
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47. Conformational Changes in the Reaction of Pyridoxal Kinase.
- Author
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Ming-hui Li, Kwok, Francis, Wen-rui Chang, Sheng-quan Liu, Lo, Samuel C. L., Ji-ping Zhang, Tao Jiang, and Dong-cai Liang
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- *
VITAMIN B6 , *CONFORMATIONAL analysis , *CATALYSIS , *ENZYMES , *BINDING sites , *BIOCHEMISTRY - Abstract
To understand the processes involved in the catalytic mechanism of pyridoxal kinase (PLK),1 we determined the crystal structures of PLK-AMP-PCP-pyridoxamine, PLK·ADP·PLP, and PLK·ADP complexes. Comparisons of these structures have revealed that PLK exhibits different conformations during its catalytic process. After the binding of AMP-PCP (an analogue that replaced ATP) and pyridoxamine to PLK, this enzyme retains a conformation similar to that of the PLK·ATP complex. The distance between the reacting groups of the two substrates is 5.8 Å apart, indicating that the position of ATP is not favorable to spontaneous transfer of its phosphate group. However, the structure of PLK·ADP·PLP complex exhibited significant changes in both the conformation of the enzyme and the location of the ligands at the active site. Therefore, it appears that after binding of both substrates, the enzyme-substrate complex requires changes in the protein structure to enable the transfer of the phosphate group from ATP to vitamin B6. Furthermore, a conformation of the enzyme-substrate complex before the transition state of the enzymatic reaction was also hypothesized. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
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