Unexpected Deacetylation Mechanism Suggested by a Density Functional Theory QM/MM Study of Histone-Deacetylase-Like Protein
2006
Abstract
To characterize the catalytic mechanism for zinc-dependent histone deacetylases (HDAC), we have carried out d. functional theory (DFT) QM/MM studies on the deacetylation reaction catalyzed by a histone-deacetylase-like protein (HDLP). The calcn. results do not support the previous mechanistic hypothesis, but suggest a lower protonation state for the active site as well as a 4-fold zinc coordination during the reaction process. To characterize such mechanistic difference is not only significant for our fundamental understanding of its inner workings but also crucial for the design of HDAC inhibitors. [on SciFinder (R)]
Details
Title
Unexpected Deacetylation Mechanism Suggested by a Density Functional Theory QM/MM Study of Histone-Deacetylase-Like Protein
Author(s)
Corminboeuf, Clemence ; Hu, Po ; Tuckerman, Mark E. ; Zhang, Yingkai
Published in
Journal of the American Chemical Society
Volume
128
Issue
14
Pages
4530-4531
Date
2006
ISSN
0002-7863
Keywords
Protonation (DFT QM/MM anal. addresses active site protonation state and zinc coordination in novel deacetylation mechanism for histone-deacetylase-like protein); Proteins Role: BSU (Biological study; unclassified); BIOL (Biological study) (HDLP (histone-deacetylase-like protein); DFT QM/MM anal. addresses active site protonation state and zinc coordination in novel deacetylation mechanism for histone-deacetylase-like protein); Enzyme functional sites (active; DFT QM/MM anal. addresses active site protonation state and zinc coordination in novel deacetylation mechanism for histone-deacetylase-like protein); Complexation (zinc; DFT QM/MM anal. addresses active site protonation state and zinc coordination in novel deacetylation mechanism for histone-deacetylase-like protein); histone deacetylase HDLP protein deacetylation mechanism calcn
Note
CAN 144:345770
7-4
Enzymes
Department of Chemistry,New York University,New York,NY,USA.
Journal
written in English.
7440-66-6 (Zinc); 9076-57-7 (Histone deacetylase) Role: BSU (Biological study, unclassified), BIOL (Biological study) (DFT QM/MM anal. addresses active site protonation state and zinc coordination in novel deacetylation mechanism for histone-deacetylase-like protein); 60-18-4 (L-Tyrosine); 71-00-1 (L-Histidine) Role: BSU (Biological study, unclassified), BIOL (Biological study) (catalytic role; DFT QM/MM anal. addresses active site protonation state and zinc coordination in novel deacetylation mechanism for histone-deacetylase-like protein)
7-4
Enzymes
Department of Chemistry,New York University,New York,NY,USA.
Journal
written in English.
7440-66-6 (Zinc); 9076-57-7 (Histone deacetylase) Role: BSU (Biological study, unclassified), BIOL (Biological study) (DFT QM/MM anal. addresses active site protonation state and zinc coordination in novel deacetylation mechanism for histone-deacetylase-like protein); 60-18-4 (L-Tyrosine); 71-00-1 (L-Histidine) Role: BSU (Biological study, unclassified), BIOL (Biological study) (catalytic role; DFT QM/MM anal. addresses active site protonation state and zinc coordination in novel deacetylation mechanism for histone-deacetylase-like protein)
Laboratories
LCMD
Record Appears in
Scientific production and competences > SB - School of Basic Sciences > ISIC - Institute of Chemical Sciences and Engineering > LCMD - Laboratory of Computational Molecular Design
Peer-reviewed publications
Work outside EPFL
Journal Articles
Published
Peer-reviewed publications
Work outside EPFL
Journal Articles
Published
Record creation date
2007-10-22