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1yc3

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[[Image:1yc3.gif|left|200px]]<br /><applet load="1yc3" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1yc3.gif|left|200px]]
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caption="1yc3, resolution 2.12&Aring;" />
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'''Crystal Structure of human HSP90alpha complexed with dihydroxyphenylpyrazoles'''<br />
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{{Structure
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|PDB= 1yc3 |SIZE=350|CAPTION= <scene name='initialview01'>1yc3</scene>, resolution 2.12&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=4BC:4-(1,3-BENZODIOXOL-5-YL)-5-(5-ETHYL-2,4-DIHYDROXYPHENYL)-2H-PYRAZOLE-3-CARBOXYLIC ACID'>4BC</scene>
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|ACTIVITY=
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|GENE= HSPCA, HSP90A, HSPC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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}}
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'''Crystal Structure of human HSP90alpha complexed with dihydroxyphenylpyrazoles'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1YC3 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 <scene name='pdbligand=4BC:'>4BC</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YC3 OCA].
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1YC3 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=1YC3 OCA].
==Reference==
==Reference==
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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://ispc.weizmann.ac.il//pmbin/getpm?pmid=15713410 15713410]
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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]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:03:49 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:20:59 2008''

Revision as of 13:21, 20 March 2008


PDB ID 1yc3

Drag the structure with the mouse to rotate
, resolution 2.12Å
Ligands:
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

1YC3 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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