8 results on '"Allali-Hassani A"'
Search Results
2. Structural Biology of Human H3K9 Methyltransferases
- Author
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Wu, Hong, primary, Min, Jinrong, additional, Lunin, Vladimir V., additional, Antoshenko, Tatiana, additional, Dombrovski, Ludmila, additional, Zeng, Hong, additional, Allali-Hassani, Abdellah, additional, Campagna-Slater, Valérie, additional, Vedadi, Masoud, additional, Arrowsmith, Cheryl H., additional, Plotnikov, Alexander N., additional, and Schapira, Matthieu, additional
- Published
- 2010
- Full Text
- View/download PDF
3. Structural Studies of a Four-MBT Repeat Protein MBTD1
- Author
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Eryilmaz, Jitka, primary, Pan, Patricia, additional, Amaya, Maria F., additional, Allali-Hassani, Abdellah, additional, Dong, Aiping, additional, Adams-Cioaba, Melanie A., additional, MacKenzie, Farrell, additional, Vedadi, Masoud, additional, and Min, Jinrong, additional
- Published
- 2009
- Full Text
- View/download PDF
4. Structural Biology of Human H3K9 Methyltransferases
- Author
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Jinrong Min, Cheryl H. Arrowsmith, Masoud Vedadi, Hong Wu, Valérie Campagna-Slater, Hong Zeng, Alexander N. Plotnikov, Matthieu Schapira, Abdellah Allali-Hassani, Ludmila Dombrovski, Vladimir V. Lunin, and Tatiana Antoshenko
- Subjects
Models, Molecular ,Methyltransferase ,Protein Conformation ,Static Electricity ,lcsh:Medicine ,Biochemistry ,Histone-Lysine N-Methyltransferase ,Substrate Specificity ,03 medical and health sciences ,0302 clinical medicine ,Protein structure ,Biochemistry/Protein Chemistry ,Genetics and Genomics/Epigenetics ,Catalytic Domain ,Humans ,lcsh:Science ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,biology ,Biochemistry/Structural Genomics ,lcsh:R ,Methylation ,Enzyme structure ,Histone ,Structural biology ,030220 oncology & carcinogenesis ,Histone methyltransferase ,Histone Methyltransferases ,biology.protein ,lcsh:Q ,Crystallization ,Research Article - Abstract
SET domain methyltransferases deposit methyl marks on specific histone tail lysine residues and play a major role in epigenetic regulation of gene transcription. We solved the structures of the catalytic domains of GLP, G9a, Suv39H2 and PRDM2, four of the eight known human H3K9 methyltransferases in their apo conformation or in complex with the methyl donating cofactor, and peptide substrates. We analyzed the structural determinants for methylation state specificity, and designed a G9a mutant able to tri-methylate H3K9. We show that the I-SET domain acts as a rigid docking platform, while induced-fit of the Post-SET domain is necessary to achieve a catalytically competent conformation. We also propose a model where long-range electrostatics bring enzyme and histone substrate together, while the presence of an arginine upstream of the target lysine is critical for binding and specificity. Enhanced version This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.
- Published
- 2010
- Full Text
- View/download PDF
5. Structural Studies of a Four-MBT Repeat Protein MBTD1
- Author
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Jinrong Min, Jitka Eryilmaz, Maria F. Amaya, Aiping Dong, Abdellah Allali-Hassani, Masoud Vedadi, Patricia W. Pan, Farrell MacKenzie, and Melanie A. Adams-Cioaba
- Subjects
animal structures ,Chromosomal Proteins, Non-Histone ,Protein Conformation ,Stereochemistry ,Molecular Sequence Data ,Molecular Conformation ,Polycomb-Group Proteins ,lcsh:Medicine ,Sequence alignment ,Arginine ,Methylation ,DNA-binding protein ,Histones ,03 medical and health sciences ,0302 clinical medicine ,Protein structure ,Humans ,Nucleosome ,Amino Acid Sequence ,lcsh:Science ,Biochemistry/Biomacromolecule-Ligand Interactions ,Peptide sequence ,030304 developmental biology ,Genetics ,0303 health sciences ,Multidisciplinary ,Sequence Homology, Amino Acid ,biology ,Lysine ,lcsh:R ,Chromatin ,Nucleosomes ,Protein Structure, Tertiary ,Repressor Proteins ,Histone ,030220 oncology & carcinogenesis ,biology.protein ,lcsh:Q ,Biochemistry/Transcription and Translation ,Protein Processing, Post-Translational ,Research Article ,Developmental Biology - Abstract
Background: The Polycomb group (PcG) of proteins is a family of important developmental regulators. The respective members function as large protein complexes involved in establishment and maintenance of transcriptional repression of developmental control genes. MBTD1, Malignant Brain Tumor domain-containing protein 1, is one such PcG protein. MBTD1 contains four MBT repeats. Methodology/Principal Findings: We have determined the crystal structure of MBTD1 (residues 130–566aa covering the 4 MBT repeats) at 2.5 A u resolution by X-ray crystallography. The crystal structure of MBTD1 reveals its similarity to another four-MBT-repeat protein L3MBTL2, which binds lower methylated lysine histones. Fluorescence polarization experiments confirmed that MBTD1 preferentially binds mono- and di-methyllysine histone peptides, like L3MBTL1 and L3MBTL2. All known MBT-peptide complex structures characterized to date do not exhibit strong histone peptide sequence selectivity, and use a ‘‘cavity insertion recognition mode’’ to recognize the methylated lysine with the deeply buried methyl-lysine forming extensive interactions with the protein while the peptide residues flanking methyl-lysine forming very few contacts [1]. Nevertheless, our mutagenesis data based on L3MBTL1 suggested that the histone peptides could not bind to MBT repeats in any orientation. Conclusions: The four MBT repeats in MBTD1 exhibits an asymmetric rhomboid architecture. Like other MBT repeat proteins characterized so far, MBTD1 binds mono- or dimethylated lysine histones through one of its four MBT repeats utilizing a semi-aromatic cage. Enhanced version: This article can also be viewed as an enhanced version (http://plosone.org/enhanced/pone.0007274/) in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.
- Published
- 2009
- Full Text
- View/download PDF
6. Structural Biology of Human H3K9 Methyltransferases.
- Author
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Hong Wu, Jinrong Min, Lunin, Vladimir V., Antoshenko, Tatiana, Dombrovski, Ludmila, Hong Zeng, Allali-Hassani, Abdellah, Campagna-Slater, Valérie, Vedadi, Masoud, Arrowsmith, Cheryl H., Plotnikov, Alexander N., and Schapira, Matthieu
- Subjects
TRANSMETHYLATION ,METHYLTRANSFERASES ,HIGH-lysine diet ,TRANSFERASES ,GENETICS ,AMINO acids ,LIFE sciences - Abstract
SET domain methyltransferases deposit methyl marks on specific histone tail lysine residues and play a major role in epigenetic regulation of gene transcription. We solved the structures of the catalytic domains of GLP, G9a, Suv39H2 and PRDM2, four of the eight known human H3K9 methyltransferases in their apo conformation or in complex with the methyl donating cofactor, and peptide substrates. We analyzed the structural determinants for methylation state specificity, and designed a G9a mutant able to tri-methylate H3K9. We show that the I-SET domain acts as a rigid docking platform, while induced-fit of the Post-SET domain is necessary to achieve a catalytically competent conformation. We also propose a model where long-range electrostatics bring enzyme and histone substrate together, while the presence of an arginine upstream of the target lysine is critical for binding and specificity. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
7. The crystal structure of Toxoplasma gondii pyruvate kinase 1.
- Author
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Rebecca Bakszt, Amy Wernimont, Abdellah Allali-Hassani, Man Wai Mok, Tanya Hills, Raymond Hui, and Juan C Pizarro
- Subjects
Medicine ,Science - Abstract
Pyruvate kinase (PK), which catalyzes the final step in glycolysis converting phosphoenolpyruvate to pyruvate, is a central metabolic regulator in most organisms. Consequently PK represents an attractive therapeutic target in cancer and human pathogens, like Apicomplexans. The phylum Aplicomplexa, a group of exclusively parasitic organisms, includes the genera Plasmodium, Cryptosporidium and Toxoplasma, the etiological agents of malaria, cryptosporidiosis and toxoplasmosis respectively. Toxoplasma gondii infection causes a mild illness and is a very common infection affecting nearly one third of the world's population.We have determined the crystal structure of the PK1 enzyme from T. gondii, with the B domain in the open and closed conformations. We have also characterized its enzymatic activity and confirmed glucose-6-phosphate as its allosteric activator. This is the first description of a PK enzyme in a closed inactive conformation without any bound substrate. Comparison of the two tetrameric TgPK1 structures indicates a reorientation of the monomers with a concomitant change in the buried surface among adjacent monomers. The change in the buried surface was associated with significant B domain movements in one of the interacting monomers.We hypothesize that a loop in the interface between the A and B domains plays an important role linking the position of the B domain to the buried surface among monomers through two α-helices. The proposed model links the catalytic cycle of the enzyme with its domain movements and highlights the contribution of the interface between adjacent subunits. In addition, an unusual ordered conformation was observed in one of the allosteric binding domains and it is related to a specific apicomplexan insertion. The sequence and structural particularity would explain the atypical activation by a mono-phosphorylated sugar. The sum of peculiarities raises this enzyme as an emerging target for drug discovery.
- Published
- 2010
- Full Text
- View/download PDF
8. Structural studies of a four-MBT repeat protein MBTD1.
- Author
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Jitka Eryilmaz, Patricia Pan, Maria F Amaya, Abdellah Allali-Hassani, Aiping Dong, Melanie A Adams-Cioaba, Farrell Mackenzie, Masoud Vedadi, and Jinrong Min
- Subjects
Medicine ,Science - Abstract
The Polycomb group (PcG) of proteins is a family of important developmental regulators. The respective members function as large protein complexes involved in establishment and maintenance of transcriptional repression of developmental control genes. MBTD1, Malignant Brain Tumor domain-containing protein 1, is one such PcG protein. MBTD1 contains four MBT repeats.We have determined the crystal structure of MBTD1 (residues 130-566aa covering the 4 MBT repeats) at 2.5 A resolution by X-ray crystallography. The crystal structure of MBTD1 reveals its similarity to another four-MBT-repeat protein L3MBTL2, which binds lower methylated lysine histones. Fluorescence polarization experiments confirmed that MBTD1 preferentially binds mono- and di-methyllysine histone peptides, like L3MBTL1 and L3MBTL2. All known MBT-peptide complex structures characterized to date do not exhibit strong histone peptide sequence selectivity, and use a "cavity insertion recognition mode" to recognize the methylated lysine with the deeply buried methyl-lysine forming extensive interactions with the protein while the peptide residues flanking methyl-lysine forming very few contacts [1]. Nevertheless, our mutagenesis data based on L3MBTL1 suggested that the histone peptides could not bind to MBT repeats in any orientation.The four MBT repeats in MBTD1 exhibits an asymmetric rhomboid architecture. Like other MBT repeat proteins characterized so far, MBTD1 binds mono- or dimethylated lysine histones through one of its four MBT repeats utilizing a semi-aromatic cage.This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.
- Published
- 2009
- Full Text
- View/download PDF
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