4bqj
From Proteopedia
structure of HSP90 with an inhibitor bound
Structural highlights
FunctionHS90A_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.[1] [2] Publication Abstract from PubMedNovel 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Homo sapiens | Large Structures | Amboldi N | Bindi S | Brasca MG | Caronni D | Casale E | Ceccarelli W | Colombo N | DePonti A | Donati D | Ermoli A | Fachin G | Felder ER | Ferguson RD | Fiorelli C | Fogliatto G | Guanci M | Isacchi A | Mantegani S | Pesenti E | Polucci P | Riceputi L | Sola F | Visco C | Zuccotto F
