Binding of N⁸-Acetylspermidine Analogues to Histone Deacetylase 10 Reveals Molecular Strategies for Blocking Polyamine Deacetylation.

ABSTRACT: Eukaryotic histone deacetylase 10 (HDAC10) is a Zn²⁺-dependent hydrolase that exhibits catalytic specificity for the hydrolysis of the polyamine N⁸-acetylspermidine. The recently determined crystal structure of HDAC10 from Danio rerio (zebrafish) reveals a narrow active site cleft and a negatively charged "gatekeeper" (E274) that favors the binding of the slender cationic substrate. Because HDAC10 expression is upregulated in advanced-stage neuroblastoma and induces autophagy, the selective inhibition of HDAC10 suppresses the autophagic response and renders cancer cells more susceptible to cytotoxic chemotherapeutic drugs. Here, we describe X-ray crystal structures of zebrafish HDAC10 complexed with eight different analogues of N⁸-acety

SUBMITTER: Herbst-Gervasoni CJ 

PROVIDER: S-EPMC6904438 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature