title: Theoretical study revealing the functioning of a novel combination of catalytic motifs in histone deacetylase.
abstract: Histone deacetylases (HDACs) have recently attracted considerable interest as targets in the treatment of cell proliferative diseases such as cancer. In the present work, the chemical properties of the active site of HDAC were theoretically investigated at a high computational level. Evidence was gathered for a novel catalytic mechanism, which differs from a previous proposal in the native protonation state of the His-Asp dyads, and in the deprotonation of water as a distinct step in the mechanism.
authors.affiliation: General Chemistry Group, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium. kenno.vanommeslaeghe@vub.ac.be
authors.forename: K
authors.initials: K
authors.lastname: Vanommeslaeghe
authors.forename: F
authors.initials: F
authors.lastname: De Proft
authors.forename: S
authors.initials: S
authors.lastname: Loverix
authors.forename: D
authors.initials: D
authors.lastname: Tourwé
authors.forename: P
authors.initials: P
authors.lastname: Geerlings
mesh_terms: D020816:Amino Acid Motifs; D000970:Antineoplastic Agents / Q000737:chemistry*; D001224:Aspartic Acid; D001665:Binding Sites; D002384:Catalysis; D020134:Catalytic Domain; D006639:Histidine; D006655:Histone Deacetylases / Q000737:chemistry*; D008958:Models, Molecular; D011522:Protons; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D011522:Protons; D014867:Water; D001224:Aspartic Acid; D006639:Histidine; D006655:Histone Deacetylases