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spinqualitylabelsall models PDB ID 1yc3 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, resolution 2.12Å
Ligands:
Gene:	HSPCA, HSP90A, HSPC1 (Homo sapiens)
Related:	1YC1, 1YC4
Resources:	FirstGlance, OCA, PDBsum, RCSB
Coordinates:	save as pdb, mmCIF, xml

Crystal Structure of human HSP90alpha complexed with dihydroxyphenylpyrazoles

Overview

A series of dihydroxyphenylpyrazole compounds were identified as a unique class of reversible Hsp90 inhibitors. The crystal structures for two of the identified compounds complexed with the N-terminal ATP binding domain of human Hsp90alpha were determined. The dihydroxyphenyl ring of the compounds fits deeply into the adenine binding pocket with the C2 hydroxyl group forming a direct hydrogen bond with the side chain of Asp93. The pyrazole ring forms hydrogen bonds to the backbone carbonyl of Gly97, the hydroxyl group of Thr184 and to a water molecule, which is present in all of the published HSP90 structures. One of the identified compounds (G3130) demonstrated cellular activities (in Her-2 degradation and activation of Hsp70 promoter) consistent with the inhibition of cellular Hsp90 functions.

About this Structure

1YC3 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Crystal structures of human HSP90alpha-complexed with dihydroxyphenylpyrazoles., Kreusch A, Han S, Brinker A, Zhou V, Choi HS, He Y, Lesley SA, Caldwell J, Gu XJ, Bioorg Med Chem Lett. 2005 Mar 1;15(5):1475-8. PMID:15713410

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