1uy8: Difference between revisions
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==Overview== | ==Overview== | ||
Inhibition of the ATPase activity of the chaperone protein HSP90 is a | 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== | ||
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[[Category: Fink, A.]] | [[Category: Fink, A.]] | ||
[[Category: Fromont, C.]] | [[Category: Fromont, C.]] | ||
[[Category: Hubbard, R | [[Category: Hubbard, R E.]] | ||
[[Category: Massey, A.]] | [[Category: Massey, A.]] | ||
[[Category: Sharp, S.]] | [[Category: Sharp, S.]] | ||
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[[Category: pu5]] | [[Category: pu5]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:29:37 2008'' | ||