2v5w

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spinqualitylabelsall models 2v5w, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CRYSTAL STRUCTURE OF HDAC8-SUBSTRATE COMPLEX

Overview

Histone deacetylases (HDACs)-an enzyme family that deacetylates histones, and non-histone proteins-are implicated in human diseases such as cancer, and the first-generation of HDAC inhibitors are now in clinical trials., Here, we report the 2.0 A resolution crystal structure of a catalytically, inactive HDAC8 active-site mutant, Tyr306Phe, bound to an acetylated, peptidic substrate. The structure clarifies the role of active-site, residues in the deacetylation reaction and substrate recognition. Notably, the structure shows the unexpected role of a conserved residue at the, active-site rim, Asp 101, in positioning the substrate by directly, interacting with the peptidic backbone and imposing a constrained, cis-conformation. A similar interaction is observed in a new hydroxamate, ... [(full description)]

About this Structure

2V5W is a [Single protein] structure of sequence from [Homo sapiens] with K, ZN, ACE and MCM as [ligands]. Structure known Active Site: AC1. Full crystallographic information is available from [OCA].

Reference

Substrate binding to histone deacetylases as shown by the crystal structure of the HDAC8-substrate complex., Vannini A, Volpari C, Gallinari P, Jones P, Mattu M, Carfi A, De Francesco R, Steinkuhler C, Di Marco S, EMBO Rep. 2007 Sep;8(9):879-84. Epub 2007 Aug 10. PMID:17721440

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