2xjg

Structure of HSP90 with small molecule inhibitor bound

spinqualitylabelsall models 2xjg, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2xjg is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: XJG Related: 1yes, 1uy9, 2cdd, 1byq, 1osf, 2bsm, 2wi3, 1uy8, 2bug, 2wi4, 2uwd, 2wi7, 2xhx, 2bt0, 1yer, 2xdu, 1uyg, 2ccu, 2bz5, 2xds, 2xdx, 2ccs, 1uyf, 1uyi, 1yc3, 1uyd, 2byi, 2xdl, 2wi2, 1uy6, 2vci, 2wi1, 2vcj, 1yc4, 2c2l, 2fwz, 2xdk, 1uyh, 1uyk, 2cct, 2fwy, 1uye, 1uyl, 2xab, 2wi6, 1yc1, 2xhr, 2xht, 1uyc, 1uy7, 1yet, 2jjc, 2byh, 2wi5, 2xjk, 2xjj, 2xjl Resources: FirstGlance, OCA, RCSB, PDBsum Function [HS90A_HUMAN] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Inhibitors of the molecular chaperone heat shock protein 90 (Hsp90) are currently generating significant interest in clinical development as potential treatments for cancer. In a preceding publication (DOI: 10.1021/jm100059d ) we describe Astex's approach to screening fragments against Hsp90 and the subsequent optimization of two hits into leads with inhibitory activities in the low nanomolar range. This paper describes the structure guided optimization of the 2,4-dihydroxybenzamide lead molecule 1 and details some of the drug discovery strategies employed in the identification of AT13387 (35), which has progressed through preclinical development and is currently being tested in man. Discovery of (2,4-Dihydroxy-5-isopropylphenyl)-[5-(4-methylpiperazin-1-ylmethyl)-1,3-di hydroisoindol-2-yl]methanone (AT13387), a Novel Inhibitor of the Molecular Chaperone Hsp90 by Fragment Based Drug Design.,Woodhead AJ, Angove H, Carr MG, Chessari G, Congreve M, Coyle JE, Cosme J, Graham B, Day PJ, Downham R, Fazal L, Feltell R, Figueroa E, Frederickson M, Lewis J, McMenamin R, Murray CW, O'Brien MA, Parra L, Patel S, Phillips T, Rees DC, Rich S, Smith DM, Trewartha G, Vinkovic M, Williams B, Woolford AJ J Med Chem. 2010 Jul 28. PMID:20662534 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Heat Shock Proteins

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