Structural and Functional Influence of the Glycine-Rich Loop G³⁰²GGGY on the Catalytic Tyrosine of Histone Deacetylase 8.

ABSTRACT: Histone deacetylase 8 (HDAC8) catalyzes the hydrolysis of acetyl-l-lysine to yield products l-lysine and acetate through a mechanism in which a nucleophilic water molecule is activated by a histidine general base and a catalytic metal ion (Zn²⁺ or Fe²⁺). Acetyl-l-lysine also requires activation by metal coordination and a hydrogen bond with catalytic tyrosine Y306, which also functions in transition state stabilization. Interestingly, Y306 is located in the conserved glycine-rich loop G³⁰²GGGY. The potential flexibility afforded by the tetraglycine segment may facilitate induced-fit conformational changes in Y306 between "in" and "out" positions, as observed in related deacetylases. To probe the catalytic importance of the glycine-rich loop in HDAC8, we rig

SUBMITTER: Porter NJ 

PROVIDER: S-EPMC5161102 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature