1yc3 | pdb_00001yc3
Crystal Structure of human HSP90alpha complexed with dihydroxyphenylpyrazoles
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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 with 4BC as ligand. 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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