3o0i

Structure of the human Hsp90-alpha N-domain bound to the hsp90 inhibitor PU-H54

spinqualitylabelsall models 3o0i, resolution 1.47Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3o0i 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: P54 Related: 3c11 Gene: HSP90AA1 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Although the Hsp90 chaperone family, comprised in humans of four paralogs, Hsp90alpha, Hsp90beta, Grp94 and Trap-1, has important roles in malignancy, the contribution of each paralog to the cancer phenotype is poorly understood. This is in large part because reagents to study paralog-specific functions in cancer cells have been unavailable. Here we combine compound library screening with structural and computational analyses to identify purine-based chemical tools that are specific for Hsp90 paralogs. We show that Grp94 selectivity is due to the insertion of these compounds into a new allosteric pocket. We use these tools to demonstrate that cancer cells use individual Hsp90 paralogs to regulate a client protein in a tumor-specific manner and in response to proteome alterations. Finally, we provide new mechanistic evidence explaining why selective Grp94 inhibition is particularly efficacious in certain breast cancers. Paralog-selective Hsp90 inhibitors define tumor-specific regulation of HER2.,Patel PD, Yan P, Seidler PM, Patel HJ, Sun W, Yang C, Que NS, Taldone T, Finotti P, Stephani RA, Gewirth DT, Chiosis G Nat Chem Biol. 2013 Sep 1. doi: 10.1038/nchembio.1335. PMID:23995768 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Heat Shock Protein structures

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