2iws: Difference between revisions
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==Overview== | ==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, ... | 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== | ==About this Structure== | ||
2IWS is a | 2IWS 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 NP4 as [http://en.wikipedia.org/wiki/ligand ligand]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2IWS OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: nucleotide-binding]] | [[Category: nucleotide-binding]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 13:23:29 2007'' | ||
