X-ray Crystallographic Snapshots of Substrate Binding in the Active Site of Histone Deacetylase 10.

ABSTRACT: Histone deacetylase 10 (HDAC10) is a zinc-dependent polyamine deacetylase enriched in the cytosol of eukaryotic cells. The active site of HDAC10 contains catalytic residues conserved in other HDAC isozymes that function as lysine deacetylases: Y307 assists the zinc ion in polarizing the substrate carbonyl for nucleophilic attack, and the H136-H137 dyad serves general base-general acid functions. As an inducer of autophagy, HDAC10 is an attractive target for the design of selective inhibitors that may be useful in cancer chemotherapy. Because detailed structural information regarding the catalytic mechanism of HDAC10 may inform new approaches to inhibitor design, we now report X-ray crystal structures of HDAC10 in which reaction intermediates with substrates N⁸-acetylsperm

SUBMITTER: Herbst-Gervasoni CJ 

PROVIDER: S-EPMC8053227 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature