1uyf: Difference between revisions
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[[Image:1uyf.gif|left|200px]] | [[Image:1uyf.gif|left|200px]] | ||
'''HUMAN HSP90-ALPHA WITH 8-(2-CHLORO-3,4,5-TRIMETHOXY-BENZYL)-2-FLUORO-9-PENT-4-YLNYL-9H-PURIN-6-YLAMINE''' | {{Structure | ||
|PDB= 1uyf |SIZE=350|CAPTION= <scene name='initialview01'>1uyf</scene>, resolution 2.00Å | |||
|SITE= <scene name='pdbsite=AC1:Pu1+Binding+Site+For+Chain+A'>AC1</scene> | |||
|LIGAND= <scene name='pdbligand=PU1:8-(2-CHLORO-3,4,5-TRIMETHOXY-BENZYL)-2-FLUORO-9-PENT-4-YLNYL-9H-PURIN-6-YLAMINE'>PU1</scene> | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''HUMAN HSP90-ALPHA WITH 8-(2-CHLORO-3,4,5-TRIMETHOXY-BENZYL)-2-FLUORO-9-PENT-4-YLNYL-9H-PURIN-6-YLAMINE''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1UYF is a [ | 1UYF is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UYF OCA]. | ||
==Reference== | ==Reference== | ||
Structure-activity relationships in purine-based inhibitor binding to HSP90 isoforms., Wright L, Barril X, Dymock B, Sheridan L, Surgenor A, Beswick M, Drysdale M, Collier A, Massey A, Davies N, Fink A, Fromont C, Aherne W, Boxall K, Sharp S, Workman P, Hubbard RE, Chem Biol. 2004 Jun;11(6):775-85. PMID:[http:// | Structure-activity relationships in purine-based inhibitor binding to HSP90 isoforms., Wright L, Barril X, Dymock B, Sheridan L, Surgenor A, Beswick M, Drysdale M, Collier A, Massey A, Davies N, Fink A, Fromont C, Aherne W, Boxall K, Sharp S, Workman P, Hubbard RE, Chem Biol. 2004 Jun;11(6):775-85. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15217611 15217611] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: pu1]] | [[Category: pu1]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:38:34 2008'' | ||
Revision as of 15:38, 20 March 2008
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| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN HSP90-ALPHA WITH 8-(2-CHLORO-3,4,5-TRIMETHOXY-BENZYL)-2-FLUORO-9-PENT-4-YLNYL-9H-PURIN-6-YLAMINE
OverviewOverview
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 StructureAbout this Structure
1UYF is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structure-activity relationships in purine-based inhibitor binding to HSP90 isoforms., Wright L, Barril X, Dymock B, Sheridan L, Surgenor A, Beswick M, Drysdale M, Collier A, Massey A, Davies N, Fink A, Fromont C, Aherne W, Boxall K, Sharp S, Workman P, Hubbard RE, Chem Biol. 2004 Jun;11(6):775-85. PMID:15217611
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