1yc1: Difference between revisions
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[[Image:1yc1.gif|left|200px]]<br /> | [[Image:1yc1.gif|left|200px]]<br /><applet load="1yc1" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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'''Crystal Structures of human HSP90alpha complexed with dihydroxyphenylpyrazoles'''<br /> | '''Crystal Structures 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== | ||
1YC1 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 4BC as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 1YC1 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=1YC1 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: 4BC]] | [[Category: 4BC]] | ||
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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 16:03:45 2008'' | ||
Revision as of 14:03, 21 February 2008
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Crystal Structures 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
1YC1 is a Single protein structure of sequence from Homo sapiens with 4BC 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
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