1yc4: Difference between revisions
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[[Image:1yc4.gif|left|200px]] | [[Image:1yc4.gif|left|200px]] | ||
'''Crystal structure of human HSP90alpha complexed with dihydroxyphenylpyrazoles''' | {{Structure | ||
|PDB= 1yc4 |SIZE=350|CAPTION= <scene name='initialview01'>1yc4</scene>, resolution 1.81Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=43P:4-(1H-IMIDAZOL-4-YL)-3-(5-ETHYL-2,4-DIHYDROXY-PHENYL)-1H-PYRAZOLE'>43P</scene> | |||
|ACTIVITY= | |||
|GENE= HSPCA, HSP90A, HSPC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''Crystal structure of human HSP90alpha complexed with dihydroxyphenylpyrazoles''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1YC4 is a [ | 1YC4 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=1YC4 OCA]. | ||
==Reference== | ==Reference== | ||
Crystal structures of human HSP90alpha-complexed with dihydroxyphenylpyrazoles., Kreusch A, Han S, Brinker A, Zhou V, Choi HS, He Y, Lesley SA, Caldwell J, Gu XJ, Bioorg Med Chem Lett. 2005 Mar 1;15(5):1475-8. PMID:[http:// | Crystal structures of human HSP90alpha-complexed with dihydroxyphenylpyrazoles., Kreusch A, Han S, Brinker A, Zhou V, Choi HS, He Y, Lesley SA, Caldwell J, Gu XJ, Bioorg Med Chem Lett. 2005 Mar 1;15(5):1475-8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15713410 15713410] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: drug design]] | [[Category: drug design]] | ||
''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 15:21:02 2008'' | ||
Revision as of 13:21, 20 March 2008
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| 1yc4, resolution 1.81Å | |||||||||||||
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| Ligands: | 43P | ||||||||||||
| Gene: | HSPCA, HSP90A, HSPC1 (Homo sapiens) | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Crystal structure of human HSP90alpha complexed with dihydroxyphenylpyrazoles
Overview
A series of dihydroxyphenylpyrazole compounds were identified as a unique class of reversible Hsp90 inhibitors. The crystal structures for two of the identified compounds complexed with the N-terminal ATP binding domain of human Hsp90alpha were determined. The dihydroxyphenyl ring of the compounds fits deeply into the adenine binding pocket with the C2 hydroxyl group forming a direct hydrogen bond with the side chain of Asp93. The pyrazole ring forms hydrogen bonds to the backbone carbonyl of Gly97, the hydroxyl group of Thr184 and to a water molecule, which is present in all of the published HSP90 structures. One of the identified compounds (G3130) demonstrated cellular activities (in Her-2 degradation and activation of Hsp70 promoter) consistent with the inhibition of cellular Hsp90 functions.
About this Structure
1YC4 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structures of human HSP90alpha-complexed with dihydroxyphenylpyrazoles., Kreusch A, Han S, Brinker A, Zhou V, Choi HS, He Y, Lesley SA, Caldwell J, Gu XJ, Bioorg Med Chem Lett. 2005 Mar 1;15(5):1475-8. PMID:15713410
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