1uyc: Difference between revisions
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==Overview== | ==Overview== | ||
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, . | 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. | ||
==About this Structure== | ==About this Structure== | ||
1UYC is a | 1UYC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with PU7 as [http://en.wikipedia.org/wiki/ligand ligand]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1UYC OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: pu7]] | [[Category: pu7]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 13:42:32 2007'' | ||