1UYH: Human Hsp90-alpha With 9-butyl-8-(2,5-dimethoxy-benzyl)-2-fluoro-9h- Purin-6-ylamine

Citation:
Abstract
Inhibition of the ATPase activity of the chaperone protein HSP90 is a potential strategy for treatment of cancers. We have determined structures of the HSP90alpha N-terminal domain complexed with the purine-based inhibitor, PU3, and analogs with enhanced potency both in enzyme and cell-based assays. The compounds induce upregulation of HSP70 and downregulation of the known HSP90 client proteins Raf-1, CDK4, and ErbB2, confirming that the molecules inhibit cell growth by a mechanism dependent on HSP90 inhibition. We have also determined the first structure of the N-terminal domain of HSP90beta, complexed with PU3. The structures allow a detailed rationale to be developed for the observed affinity of the PU3 class of compounds for HSP90 and also provide a structural framework for design of compounds with improved binding affinity and drug-like properties.
PDB ID: 1UYHDownload
MMDB ID: 28395
PDB Deposition Date: 2004/3/2
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 2.2  Å
Source Organism:
Similar Structures:
Biological Unit for 1UYH: monomeric; determined by author and by software (PQS)
Molecular Components in 1UYH
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.

Citing MMDB
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