2byi
3-(5-chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as Inhibitors of the Hsp90 Molecular Chaperone3-(5-chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as Inhibitors of the Hsp90 Molecular Chaperone
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] 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 PubMedInformation from X-ray crystal structures of Hsp90 inhibitors bound to the human Hsp90 molecular chaperone was used to assist in the design of 3-(5-chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as novel inhibitors of Hsp90. Accessing an extra interaction with the protein via Phe138 gave a significant increase in binding potency compared to similar analogues that do not make this interaction. 3-(5-Chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as inhibitors of the Hsp90 molecular chaperone.,Brough PA, Barril X, Beswick M, Dymock BW, Drysdale MJ, Wright L, Grant K, Massey A, Surgenor A, Workman P Bioorg Med Chem Lett. 2005 Dec 1;15(23):5197-201. Epub 2005 Oct 5. PMID:16213716[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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