1YC3: Crystal Structure Of Human Hsp90alpha Complexed With Dihydroxyphenylpyrazoles

Citation:
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.
PDB ID: 1YC3Download
MMDB ID: 32057
PDB Deposition Date: 2004/12/21
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 2.12  Å
Source Organism:
Similar Structures:
Biological Unit for 1YC3: monomeric; determined by author
Molecular Components in 1YC3
Label Count Molecule
Protein (1 molecule)
1
Heat Shock Protein HSP 90-alpha(Gene symbol: HSP90AA1)
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

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