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| [[Image:1uy8.jpg|left|200px]] | | {{Seed}} |
| | [[Image:1uy8.png|left|200px]] |
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| {{STRUCTURE_1uy8| PDB=1uy8 | SCENE= }} | | {{STRUCTURE_1uy8| PDB=1uy8 | SCENE= }} |
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| '''HUMAN HSP90-ALPHA WITH 9-BUTYL-8-(3-TRIMETHOXY-BENZYL)-9H-PURIN-6YLAMINE'''
| | ===HUMAN HSP90-ALPHA WITH 9-BUTYL-8-(3-TRIMETHOXY-BENZYL)-9H-PURIN-6YLAMINE=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_15217611}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 15217611 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_15217611}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Hsp90]] | | [[Category: Hsp90]] |
| [[Category: Pu5]] | | [[Category: Pu5]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 11:50:48 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 18:23:00 2008'' |