Unexpected Deacetylation Mechanism Suggested by a Density Functional Theory QM/MM Study of Histone-Deacetylase-Like Protein

摘要

Class I and II histone deacetylases (HDACs) constitute a very important family of zinc-dependent enzymes that catalyze the cleavage of acetyl groups from acetyl-lysine residues in histone N-terminal tails.They are critically involved in regulating chro-matin structure and gene expression,and the aberrant recruitment of HDACs has been associated with a variety of diseases,notably cancer.The detailed knowledge of their catalytic mechanism is of high importance,as HDACs have been established as very promising targets for the development of anti-tumor drugs.