Computational Analysis of Histone Deacetylase 10 Mechanism by the ONIOM Method: A Complementary Approach to X-ray and Kinetics Studies.

ABSTRACT: Histone deacetylase 10 (HDAC 10) catalyzes deacetylation of N⁸-acetylspermidine into spermidine in the cytosolic region of eukaryotic cells. Inhibition of HDAC 10 has clinical importance in certain types of cancers. Recently, X-ray crystal structures corresponding to the substrate-bound, tetrahedral intermediate-bound, and product-bound enzymes have been resolved using variant forms of humanized HDAC 10. Based on these structures, it was proposed that Y307 residue polarizes the carbonyl of the acetyl group in N⁸-acetylspermidine together with a zinc atom, which is coordinated by D174, H176, D267, and an H₂O molecule. The H₂O molecule undergoes nucleophilic addition to the carbonyl carbon of N⁸-acetylspermidine to form the tetrahedral i

SUBMITTER: Yildiz I 

PROVIDER: S-EPMC8868106 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature