1yc4
From Proteopedia
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
1YC4 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 Page seeded by OCA on Sat May 3 16:08:19 2008
Categories: Homo sapiens | Single protein | Brinker, A. | Caldwell, J. | Choi, H. | Gu, X. | Han, S. | He, Y. | Kreusch, A. | Lesley, S A. | Zhou, V. | Cancer | Cell-cycle | Drug design
