2cgf
From Proteopedia
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| - | [[Image:2cgf. | + | [[Image:2cgf.jpg|left|200px]]<br /><applet load="2cgf" size="450" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2cgf" size="450" color="white" frame="true" align="right" spinBox="true" | + | |
caption="2cgf, resolution 2.202Å" /> | caption="2cgf, resolution 2.202Å" /> | ||
'''A RADICICOL ANALOGUE BOUND TO THE ATP BINDING SITE OF THE N-TERMINAL DOMAIN OF THE YEAST HSP90 CHAPERONE'''<br /> | '''A RADICICOL ANALOGUE BOUND TO THE ATP BINDING SITE OF THE N-TERMINAL DOMAIN OF THE YEAST HSP90 CHAPERONE'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2CGF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with P2N as [http://en.wikipedia.org/wiki/ligand ligand]. | + | 2CGF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with P2N as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Site: <scene name='pdbsite=AC1:P2n Binding Site For Chain A'>AC1</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2CGF OCA]. |
==Reference== | ==Reference== | ||
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[[Category: multigene family]] | [[Category: multigene family]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 19:21:54 2007'' |
Revision as of 17:12, 18 December 2007
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A RADICICOL ANALOGUE BOUND TO THE ATP BINDING SITE OF THE N-TERMINAL DOMAIN OF THE YEAST HSP90 CHAPERONE
Overview
A series of benzo-macrolactones of varying ring size and conformation has, been prepared by chemical synthesis and evaluated by structural and, biological techniques. Thus, 12- to 16-membered lactones were obtained by, concise routes, involving ring-closing metathesis as a key step. In enzyme, assays, the 13-, 15-, and 16-membered analogs are good inhibitors, suggesting that they can adopt the required conformation to fit in the, ATP-binding site. This was confirmed by cocrystallization of 13-, 14-, and, 15-membered lactones with the N-terminal domain of yeast Hsp90, showing, that they bind similarly to the "natural" 14-membered radicicol. The most, active compounds in the ATPase assays also showed the greatest, growth-inhibitory potency in HCT116 human colon cancer cells and the, established molecular signature of Hsp90 inhibition, i.e., depletion of, client proteins with upregulation of Hsp70.
About this Structure
2CGF is a Single protein structure of sequence from Saccharomyces cerevisiae with P2N as ligand. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Inhibition of Hsp90 with synthetic macrolactones: synthesis and structural and biological evaluation of ring and conformational analogs of radicicol., Proisy N, Sharp SY, Boxall K, Connelly S, Roe SM, Prodromou C, Slawin AM, Pearl LH, Workman P, Moody CJ, Chem Biol. 2006 Nov;13(11):1203-15. PMID:17114002
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