1YC3

Crystal Structure of human HSP90alpha complexed with dihydroxyphenylpyrazoles

Summary for 1YC3

• Entry DOI: 10.2210/pdb1yc3/pdb
• Related: 1YC1 1YC4
• Descriptor: Heat shock protein HSP 90-alpha, 4-(1,3-BENZODIOXOL-5-YL)-5-(5-ETHYL-2,4-DIHYDROXYPHENYL)-2H-PYRAZOLE-3-CARBOXYLIC ACID (3 entities in total)
• Functional Keywords: cell-cycle, cancer, drug design, cell cycle
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P07900
• Total number of polymer chains: 1
• Total formula weight: 30178.62

Authors

Kreusch, A.,Han, S.,Brinker, A.,Zhou, V.,Choi, H.,He, Y.,Lesley, S.A.,Caldwell, J.,Gu, X. (deposition date: 2004-12-21, release date: 2005-02-22, Last modification date: 2024-02-14)

Primary citation

Kreusch, A.,Han, S.,Brinker, A.,Zhou, V.,Choi, H.S.,He, Y.,Lesley, S.A.,Caldwell, J.,Gu, X.J.
Crystal structures of human HSP90alpha-complexed with dihydroxyphenylpyrazoles.
Bioorg.Med.Chem.Lett., 15:1475-1478, 2005

PubMed Abstract: 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.

PubMed: 15713410
DOI: 10.1016/j.bmcl.2004.12.087

Experimental method

X-RAY DIFFRACTION (2.12 Å)