1zz3

Crystal structure of a HDAC-like protein with CypX bound

spinqualitylabelsall models 1zz3, resolution 1.76Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1zz3 is a 4 chain structure with sequence from Alcaligenaceae bacterium fb188. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 3YP, K, ZN Related: 1zz0, 1zz1 Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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