title: Unexpected deacetylation mechanism suggested by a density functional theory QM/MM study of histone-deacetylase-like protein.
abstract: To characterize the catalytic mechanism for zinc-dependent histone deacetylases (HDAC), we have carried out density functional theory QM/MM studies on the deacetylation reaction catalyzed by a histone-deacetylase-like protein (HDLP). The calculation 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.
authors.affiliation: Department of Chemistry, New York University, New York, New York 10003, USA.
authors.forename: Clémence
authors.initials: C
authors.lastname: Corminboeuf
authors.forename: Po
authors.initials: P
authors.lastname: Hu
authors.forename: Mark E
authors.initials: ME
authors.lastname: Tuckerman
authors.forename: Yingkai
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000107:Acetylation; D002384:Catalysis; D006639:Histidine / Q000737:chemistry / Q000378:metabolism; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D011789:Quantum Theory; D055672:Static Electricity; D014867:Water / Q000737:chemistry / Q000378:metabolism
chemical_list: D014867:Water; D006639:Histidine; D006655:Histone Deacetylases; D010100:Oxygen