1zz1
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Crystal structure of a HDAC-like protein with SAHA bound
OverviewOverview
Histone deacetylases (HDACs) are among the most promising targets in, cancer therapy. However, structural information greatly enhancing the, design of HDAC inhibitors as novel chemotherapeutics has not been, available on class 2 HDACs so far. Here we present the structure of the, bacterial FB188 HDAH (histone deacetylase-like amidohydrolase from, Bordetella/Alcaligenes strain FB188) that reveals high sequential and, functional homology to human class 2 HDACs. FB188 HDAH is capable to, remove the acetyl moiety from acetylated histones. Several HDAC-specific, inhibitors, which have been shown to inhibit tumor activity in both, pre-clinical models and in clinical trials, also inhibit FB188 HDAH. We, have determined the crystal structure of FB188 HDAH at a resolution of 1.6, angstroms in complex with the reaction product acetate, as well as in, complex with the inhibitors suberoylanilide hydroxamic acid (SAHA) and, cyclopentyle-propionyle hydroxamic acid (CypX) at a resolution of 1.57, angstroms and 1.75 angstroms, respectively. FB188 HDAH exhibits the, canonical fold of class 1 HDACs and contains a catalytic zinc ion. The, highest structural diversity compared to class 1 enzymes is found in loop, regions especially in the area around the entrance of the active site, indicating significant differences among the acetylated proteins binding, to class 1 and 2 HDACs, respectively.
About this StructureAbout this Structure
1ZZ1 is a Single protein structure of sequence from Bordetella sp. with ZN, K and SHH as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of a bacterial class 2 histone deacetylase homologue., Nielsen TK, Hildmann C, Dickmanns A, Schwienhorst A, Ficner R, J Mol Biol. 2005 Nov 18;354(1):107-20. Epub 2005 Oct 7. PMID:16242151
Page seeded by OCA on Wed Nov 21 07:45:10 2007