10 results on '"Vladislav A. Lushpa"'
Search Results
2. Peptides from the Sea Anemone Metridium senile with Modified Inhibitor Cystine Knot (ICK) Fold Inhibit Nicotinic Acetylcholine Receptors
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Igor E. Kasheverov, Yulia A. Logashina, Fedor D. Kornilov, Vladislav A. Lushpa, Ekaterina E. Maleeva, Yuliya V. Korolkova, Jinpeng Yu, Xiaopeng Zhu, Dongting Zhangsun, Sulan Luo, Klara Stensvåg, Denis S. Kudryavtsev, Konstantin S. Mineev, and Yaroslav A. Andreev
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Health, Toxicology and Mutagenesis ,sea anemone venom ,Metridium senile ,ICK fold peptides ,nicotinic acetylcholine receptors ,NMR structure ,electrophysiology ,radioligand assay ,Toxicology - Abstract
Nicotinic acetylcholine receptors (nAChRs) play an important role in the functioning of the central and peripheral nervous systems, and other organs of living creatures. There are several subtypes of nAChRs, and almost all of them are considered as pharmacological targets in different pathological states. The crude venom of the sea anemone Metridium senile showed the ability to interact with nAChRs. Four novel peptides (Ms11a-1–Ms11a-4) with nAChR binding activity were isolated. These peptides stabilized by three disulfide bridges have no noticeable homology with any known peptides. Ms11a-1–Ms11a-4 showed different binding activity towards the muscle-type nAChR from the Torpedo californica ray. The study of functional activity and selectivity for the most potent peptide (Ms11a-3) revealed the highest antagonism towards the heterologous rat α9α10 nAChR compared to the muscle and α7 receptors. Structural NMR analysis of two toxins (Ms11a-2 and Ms11a-3) showed that they belong to a new variant of the inhibitor cystine knot (ICK) fold but have a prolonged loop between the fifth and sixth cysteine residues. Peptides Ms11a-1–Ms11a-4 could represent new pharmacological tools since they have structures different from other known nAChRs inhibitors.
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- 2022
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3. DNA sequence-specific ligands. XX. Synthesis, spectral properties, virological and biochemical studies of fluorescent dimeric trisbenzimidazoles DB3P(n)1
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Albert F. Arutyunyan, Alexey Kostyukov, Vladislav A. Lushpa, Konstantin S. Mineev, Sergey P. Korolev, Marina B. Gottikh, Regina R. Klimova, Alla A. Kushch, Kseniya V. Kalabina, Olga Yu. Susova, and Alexei L. Zhuze
- Abstract
A new series of AT-specific minor groove DNA ligands (DB3P(n); n = 1,2,3,4) were synthesized and their spectral, biological and virological properties were investigated in water media. The variable length of methylene spacer in middle of molecule structure allows to “recognize” sequences of blocks of three AT pairs located at different distances from each other. The biological trials have shown sufficient capability to suppress activity of HIV-1 integrase catalytic activity at sub micromolar concentrations (0.25 – 0.50 µМ). DB3P(n) were found as very effective inhibitor of simplex virus type I and DNA topoisomerase I. By confocal microscopy confirmed ability of compounds stain nuclei, that can be used as gene-expression regulator.
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- 2022
4. Modulation of Toll-like receptor 1 intracellular domain structure and activity by Zn2+ ions
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Daniil Vakhrameev, Xiaohui Wang, Irina A. Talyzina, Arthur O. Zalevsky, Sergey A. Goncharuk, Mikhail B. Shevtsov, Konstantin S. Mineev, Valentin Borshchevskiy, Vladislav A. Lushpa, Alexander S. Arseniev, Marina V. Goncharuk, Aleksandra Luginina, and Cong Lin
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QH301-705.5 ,In silico ,Medicine (miscellaneous) ,medicine.disease_cause ,digestive system ,General Biochemistry, Genetics and Molecular Biology ,Article ,Protein Domains ,ddc:570 ,parasitic diseases ,Extracellular ,medicine ,Humans ,Biology (General) ,Receptor ,X-ray crystallography ,Ions ,Toll-like receptor ,Mutation ,Chemistry ,biochemical phenomena, metabolism, and nutrition ,Toll-Like Receptor 1 ,Toll-Like Receptor 2 ,Toll-like receptors ,Zinc ,HEK293 Cells ,Cytoplasm ,Biophysics ,Molecular modelling ,General Agricultural and Biological Sciences ,Solution-state NMR ,Intracellular ,Cysteine - Abstract
Toll-like receptors (TLRs) play an important role in the innate immune response. While a lot is known about the structures of their extracellular parts, many questions are still left unanswered, when the structural basis of TLR activation is analyzed for the TLR intracellular domains. Here we report the structure and dynamics of TLR1 toll-interleukin like (TIR) cytoplasmic domain in crystal and in solution. We found that the TLR1-TIR domain is capable of specific binding of Zn with nanomolar affinity. Interactions with Zn are mediated by cysteine residues 667 and 686 and C667 is essential for the Zn binding. Potential structures of the TLR1-TIR/Zn complex were predicted in silico. Using the functional assays for the heterodimeric TLR1/2 receptor, we found that both Zn addition and Zn depletion affect the activity of TLR1, and C667A mutation disrupts the receptor activity. Analysis of C667 position in the TLR1 structure and possible effects of C667A mutation, suggests that zinc-binding ability of TLR1-TIR domain is critical for the receptor activation., Lushpa et al report the structure and dynamics of the TLR1 toll-interleukin like (TIR) cytoplasmic domain in both crystal and solution. They demonstrate that the TLR1 TIR domain is capable of specific binding of Zn with nanomolar affinity, which appears to be critical for receptor activation, and provide potential structures TLR1-TIR/Zn complex based on in silico data.
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- 2021
5. 1,5-Hydride-Shift-Triggered Cyclization for the Synthesis of Unsymmetric Julolidines
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Viktoria A. Ikonnikova, Nadezhda S. Baleeva, Pavel N. Solyev, Vladislav A. Lushpa, Andrey A. Mikhaylov, Alexander A. Korlyukov, Mikhail S. Baranov, Alexander D. Volodin, and Vasilissa V. Shirokova
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chemistry.chemical_compound ,Scope (project management) ,Chemistry ,Hydride ,Organic Chemistry ,chemistry.chemical_element ,Scandium ,Trifluoromethanesulfonate ,Julolidine ,Combinatorial chemistry ,Catalysis - Abstract
Directly accessible 8-substituted tetrahydroquinolines undergo 1,5-hydride-shift-triggered cyclization to provide difficult to access julolidine derivatives in yields of 21–98% under scandium(III) triflate catalysis. Additionally, the scope of the reaction, several follow-up transformations and a remarkable side process discovered during optimization of the conditions are highlighted.
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- 2021
6. Imidazolone-activated donor-acceptor cyclopropanes with a peripheral stereocenter. A study on stereoselectivity of cycloaddition with aldehydes
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Vladislav А. Lushpa, Andrei V. Kuleshov, Mikhail S. Baranov, Aleksander А. Korlyukov, Pavel N. Solyev, Andrey А. Mikhaylov, and Vadim S. Kublitskii
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010405 organic chemistry ,Cyclopropanation ,Chemistry ,Stereochemistry ,Organic Chemistry ,Diastereomer ,010402 general chemistry ,01 natural sciences ,Cycloaddition ,0104 chemical sciences ,Cyclopropane ,Stereocenter ,chemistry.chemical_compound ,Nucleophile ,Stereoselectivity ,Donor acceptor - Abstract
Nucleophilic cyclopropanation of arylideneimidazolones possessing a peripheral chiral center and the subsequent fractional crystallization of diastereomers allows access to the compounds with an enantiomerically uniform configuration of the spirocyclic donoracceptor cyclopropane fragment. They were used to study the mechanism of the cycloaddition reaction with aldehydes; it was demonstrated that stereochemical information from the cyclopropane fragment is lost during the reaction.
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- 2020
7. Spatial Structure of NanoFAST in the Apo State and in Complex with its Fluorogen HBR-DOM2
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Vladislav A. Lushpa, Nadezhda S. Baleeva, Sergey A. Goncharuk, Marina V. Goncharuk, Alexander S. Arseniev, Mikhail S. Baranov, and Konstantin S. Mineev
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Magnetic Resonance Spectroscopy ,Rhodanine ,Organic Chemistry ,Proteins ,Hydrogen Bonding ,General Medicine ,Ligands ,Catalysis ,Computer Science Applications ,Inorganic Chemistry ,fluorogen-activating protein ,FAST ,nanoFAST ,spatial structure ,dynamics ,ligand specificity ,fluorogen ,binding constant ,structure ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy - Abstract
NanoFAST is a fluorogen-activating protein and can be considered one of the smallest encodable fluorescent tags. Being a shortened variant of another fluorescent tag, FAST, nanoFAST works nicely only with one out of all known FAST ligands. This substantially limits the applicability of this protein. To find the reason for such a behavior, we investigated the spatial structure and dynamics of nanoFAST, both in the apo state and in the complex with its fluorogen molecule, using the solution NMR spectroscopy. We showed that the truncation of FAST did not affect the structure of the remaining part of the protein. Our data suggest that the deleted N-terminus of FAST destabilizes the C-terminal domain in the apo state. While it does not contact the fluorogen directly, it serves as a free energy reservoir that enhances the ligand binding propensity of the protein. The structure of nanoFAST/HBR-DOM2 complex reveals the atomistic details of nanoFAST interactions with the rhodanine-based ligands and explains the ligand specificity. NanoFAST selects ligands with the lowest dissociation constants, 2,5-disubstituted 4-hydroxybenzyldienerhodainines, which allow the non-canonical intermolecular CH–N hydrogen bonding and provide the optimal packing of the ligand within the hydrophobic cavity of the protein.
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- 2022
8. New Insectotoxin from Tibellus Oblongus Spider Venom Presents Novel Adaptation of ICK Fold
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Fedor Kornilov, Steve Peigneur, Elizaveta M. Solovyeva, Jan Tytgat, Alexander Mikov, Konstantin S. Mineev, Sergey A. Kozlov, Anna A. Lobas, Ekaterina E. Maleeva, Yuliya V. Korolkova, Vladislav A. Lushpa, Mikhail V. Gorshkov, and Yaroslav A. Andreev
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Proteomics ,Protein Folding ,DNA, Complementary ,Protein Conformation ,Health, Toxicology and Mutagenesis ,proteome ,lcsh:Medicine ,Spider Venoms ,Venom ,Peptide ,Toxicology ,Article ,ICK fold ,03 medical and health sciences ,0302 clinical medicine ,Complementary DNA ,Houseflies ,Animals ,Amino Acid Sequence ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,biology ,Base Sequence ,Tibellus oblongus ,Chemistry ,spider venom ,lcsh:R ,Protein primary structure ,Spiders ,biology.organism_classification ,Biochemistry ,Gene Expression Regulation ,Larva ,NMR structure ,Inhibitor cystine knot ,Thioredoxin ,Transcriptome ,insectotoxin ,transcriptome ,030217 neurology & neurosurgery ,Cysteine - Abstract
The Tibellus oblongus spider is an active predator that does not spin webs and remains poorly investigated in terms of venom composition. Here, we present a new toxin, named Tbo-IT2, predicted by cDNA analysis of venom glands transcriptome. The presence of Tbo-IT2 in the venom was confirmed by proteomic analyses using the LC-MS and MS/MS techniques. The distinctive features of Tbo-IT2 are the low similarity of primary structure with known animal toxins and the unusual motif of 10 cysteine residues distribution. Recombinant Tbo-IT2 (rTbo-IT2), produced in E. coli using the thioredoxin fusion protein strategy, was structurally and functionally studied. rTbo-IT2 showed insecticidal activity on larvae of the housefly Musca domestica (LD100 200 &mu, g/g) and no activity on the panel of expressed neuronal receptors and ion channels. The spatial structure of the peptide was determined in a water solution by NMR spectroscopy. The Tbo-IT2 structure is a new example of evolutionary adaptation of a well-known inhibitor cystine knot (ICK) fold to 5 disulfide bonds configuration, which determines additional conformational stability and gives opportunities for insectotoxicity and probably some other interesting features.
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- 2021
9. Sampling the cultivation parameter space for the bacterial production of TLR1 intracellular domain reveals the multiple optima
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Sergey A. Goncharuk, Vladislav A. Lushpa, Konstantin S. Mineev, Marina V. Goncharuk, and Alexander S. Arseniev
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0106 biological sciences ,Intracellular domain ,Lysis ,Gene Expression ,Parameter space ,medicine.disease_cause ,01 natural sciences ,03 medical and health sciences ,chemistry.chemical_compound ,Protein Domains ,010608 biotechnology ,Escherichia coli ,medicine ,Humans ,030304 developmental biology ,0303 health sciences ,Chemistry ,Toll-Like Receptor 1 ,Recombinant Proteins ,Yield (chemistry) ,Triton X-100 ,Biophysics ,Protein solubility ,Intracellular ,Biotechnology - Abstract
T7 expression system is an extremely popular approach for the recombinant protein production in Escherichia coli for structural and functional studies and therapeutic applications. There are many useful tools and successful techniques that allow expressing the desired protein in this system. However, high yield of soluble protein often requires a systematic optimization of a wide range of cell cultivation parameters. Here we analyze the effect of three key cultivation parameters - chemical inductor, temperature and time of post-induction culturing on the expression level of TLR1 intracellular TIR domain in a soluble form. In addition, the influence of Triton X-100 detergent on the protein solubility during the cell lysis was investigated. We show that a high expression level of the correctly folded soluble protein can be obtained under different combinations of cultivation parameters.
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- 2021
10. A Novel Lipopeptaibol Emericellipsin A with Antimicrobial and Antitumor Activity Produced by the Extremophilic Fungus Emericellopsis alkalina
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Yaroslav A. Andreev, Konstantin S. Mineev, Eugene A. Rogozhin, Anna A. Baranova, Alexey S. Vasilchenko, Anastasia V. Vasilchenko, M. E. Krasheninnikov, M. L. Georgieva, V. S. Sadykova, A. V. Lyundup, Alexander B. Kulko, and Vladislav A. Lushpa
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0301 basic medicine ,Emericellopsis alkalina ,Magnetic Resonance Spectroscopy ,Cell Survival ,emericellipsin A ,Peptaibol ,Pharmaceutical Science ,Antineoplastic Agents ,Microbial Sensitivity Tests ,Article ,Mass Spectrometry ,Analytical Chemistry ,lcsh:QD241-441 ,03 medical and health sciences ,chemistry.chemical_compound ,lcsh:Organic chemistry ,Anti-Infective Agents ,Ascomycota ,antibacterial activity ,Cell Line, Tumor ,Drug Discovery ,Humans ,Physical and Theoretical Chemistry ,Candida albicans ,Chromatography, High Pressure Liquid ,chemistry.chemical_classification ,2D structure ,biology ,Bacteria ,Molecular Structure ,Organic Chemistry ,Aspergillus niger ,antifungal activity ,Fungi ,biology.organism_classification ,Antimicrobial ,Yeast ,Amino acid ,030104 developmental biology ,chemistry ,Biochemistry ,Chemistry (miscellaneous) ,cytotoxic properties ,Molecular Medicine ,Antibacterial activity - Abstract
Soil fungi are known to contain a rich variety of defense metabolites that allow them to compete with other organisms (fungi, bacteria, nematodes, and insects) and help them occupy more preferential areas at the expense of effective antagonism. These compounds possess antibiotic activity towards a wide range of other microbes, particularly fungi that belong to different taxonomical units. These compounds include peptaibols, which are non-ribosomal synthesized polypeptides containing non-standard amino acid residues (alpha-aminoisobutyric acid mandatory) and some posttranslational modifications. We isolated a novel antibiotic peptide from the culture medium of Emericellopsis alkalina, an alkalophilic strain. This peptide, called emericellipsin A, exhibited a strong antifungal effect against the yeast Candida albicans, the mold fungus Aspergillus niger, and human pathogen clinical isolates. It also exhibited antimicrobial activity against some Gram-positive and Gram-negative bacteria. Additionally, emericellipsin A showed a significant cytotoxic effect and was highly active against Hep G2 and HeLa tumor cell lines. We used NMR spectroscopy to reveal that this peptaibol is nine amino acid residues long and contains non-standard amino acids. The mode of molecular action of emericellipsin A is most likely associated with its effects on the membranes of cells. Emericellipsin A is rather short peptaibol and could be useful for the development of antifungal, antibacterial, or anti-tumor remedies.
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- 2018
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