Theoretical study revealing the functioning of a novel combination of catalytic motifs in histone deacetylase

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.

Computational study of the active site of HDAC at a high level of theory, yielding evidence for a novel catalytic mechanism that differs from a previous proposal in the native protonation state of the enzyme, and in the deprotonation of water as a distinct step in the mechanism.Figure optionsDownload as PowerPoint slide