2iwu
From Proteopedia
OCA (Talk | contribs)
(New page: 200px<br /> <applet load="2iwu" size="450" color="white" frame="true" align="right" spinBox="true" caption="2iwu, resolution 2.8Å" /> '''ANALOGUES OF RADICIC...)
Next diff →
Revision as of 16:06, 29 October 2007
|
ANALOGUES OF RADICICOL BOUND TO THE ATP-BINDING SITE OF HSP90
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, ... [(full description)]
About this Structure
2IWU is a [Single protein] structure of sequence from [Saccharomyces cerevisiae] with NP5 as [ligand]. 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
Page seeded by OCA on Mon Oct 29 18:11:13 2007
