2cdd

File:2cdd.gif

spinqualitylabelsall models 2cdd, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

HUMAN HSP90 WITH 4-(4-(2,3-DIHYDRO-BENZOL(1,4)DIOXIN-6-YL)-5-METHYL-1H-PYRAZOL-3-YL)-6-ETHYL-BENZENE-1,3-DIOL

OverviewOverview

Hsp90 encodes a ubiquitous molecular chaperone protein conserved among, species which acts on multiple substrates, many of which are important, cell-signaling proteins. Inhibition of Hsp90 function has been promoted as, a mechanism to degrade client proteins involved in tumorigenesis and, disease progression. Several assays to monitor inhibition of Hsp90, function currently exist but are limited in their use for a drug discovery, campaign. Using data from the crystal structure of an initial hit, compound, we have developed a fluorescence polarization assay to monitor, binding of compounds to the ATP-binding site of Hsp90. This assay is very, robust (Z' > 0.9) and can detect affinity of compounds with IC50s to 40, nM. We have used this assay in conjunction with cocrystal structures of, small molecules to drive a structure-based design program aimed at the, discovery and optimization of a novel class of potent Hsp90 inhibitors.

About this StructureAbout this Structure

2CDD is a Single protein structure of sequence from Homo sapiens with CT5 as ligand. Structure known Active Site: AC1. Full crystallographic information is available from OCA.

ReferenceReference

A fluorescence polarization assay for inhibitors of Hsp90., Howes R, Barril X, Dymock BW, Grant K, Northfield CJ, Robertson AG, Surgenor A, Wayne J, Wright L, James K, Matthews T, Cheung KM, McDonald E, Workman P, Drysdale MJ, Anal Biochem. 2006 Mar 15;350(2):202-13. Epub 2006 Jan 23. PMID:16460658

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