1yc4
From Proteopedia
(New page: 200px<br /> <applet load="1yc4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yc4, resolution 1.81Å" /> '''Crystal structure o...) |
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| - | [[Image:1yc4.gif|left|200px]]<br /> | + | [[Image:1yc4.gif|left|200px]]<br /><applet load="1yc4" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1yc4" size=" | + | |
caption="1yc4, resolution 1.81Å" /> | caption="1yc4, resolution 1.81Å" /> | ||
'''Crystal structure of human HSP90alpha complexed with dihydroxyphenylpyrazoles'''<br /> | '''Crystal structure of human HSP90alpha complexed with dihydroxyphenylpyrazoles'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A series of dihydroxyphenylpyrazole compounds were identified as a unique | + | 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== | ==About this Structure== | ||
| - | 1YC4 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 43P as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1YC4 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=43P:'>43P</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YC4 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: He, Y.]] | [[Category: He, Y.]] | ||
[[Category: Kreusch, A.]] | [[Category: Kreusch, A.]] | ||
| - | [[Category: Lesley, S | + | [[Category: Lesley, S A.]] |
[[Category: Zhou, V.]] | [[Category: Zhou, V.]] | ||
[[Category: 43P]] | [[Category: 43P]] | ||
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[[Category: drug design]] | [[Category: drug design]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:03:48 2008'' |
Revision as of 14:03, 21 February 2008
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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 with as ligand. 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
Page seeded by OCA on Thu Feb 21 16:03:48 2008
Categories: Homo sapiens | Single protein | Brinker, A. | Caldwell, J. | Choi, H. | Gu, X. | Han, S. | He, Y. | Kreusch, A. | Lesley, S A. | Zhou, V. | 43P | Cancer | Cell-cycle | Drug design
