4bqj

structure of HSP90 with an inhibitor bound

spinqualitylabelsall models 4bqj, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4bqj is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: XKL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. Publication Abstract from PubMed Novel small molecule inhibitors of heat shock protein 90 (Hsp90) were discovered with the help of a fragment based drug discovery approach (FBDD) and subsequent optimization with a combination of structure guided design, parallel synthesis and application of medicinal chemistry principles. These efforts led to the identification of compound 18 (NMS-E973), which displayed significant efficacy in a human ovarian A2780 xenograft tumor model, with a mechanism of action confirmed in vivo by typical modulation of known Hsp90 client proteins, and with a favorable pharmacokinetic and safety profile. Discovery of NMS-E973 as novel, selective and potent inhibitor of heat shock protein 90 (Hsp90).,Brasca MG, Mantegani S, Amboldi N, Bindi S, Caronni D, Casale E, Ceccarelli W, Colombo N, De Ponti A, Donati D, Ermoli A, Fachin G, Felder ER, Ferguson RD, Fiorelli C, Guanci M, Isacchi A, Pesenti E, Polucci P, Riceputi L, Sola F, Visco C, Zuccotto F, Fogliatto G Bioorg Med Chem. 2013 Nov 15;21(22):7047-63. doi: 10.1016/j.bmc.2013.09.018. Epub, 2013 Sep 19. PMID:24100158 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Heat Shock Protein structures

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