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From Proteopedia
Hsp90a N-terminal inhibitor
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 PubMedThe 90 kDa heat shock protein (Hsp90) is a molecular chaperone that processes nascent polypeptides into their biologically active conformations. Many of these proteins contribute to the progression of cancer, and consequently, inhibition of the Hsp90 protein folding machinery represents an innovative approach toward cancer chemotherapy. However, clinical trials with Hsp90 N-terminal inhibitors have encountered deleterious side effects and toxicities, which appear to result from the pan -inhibition of all four Hsp90 isoforms. Therefore, the development of isoform-selective Hsp90 inhibitors is sought to delineate the pathological role played by each isoform. Herein, we describe a structure-based approach that was used to design the first Hsp90a-selective inhibitors, which exhibit > 50-fold selectivity versus other Hsp90 isoforms. Selective Inhibition of the Hsp90a isoform.,Blagg B, Mishra S, Khandelwal A, Bannerjee M, Balch M, Peng S, Davis R, Merfeld T, Menthali V, Deng J, Matts R Angew Chem Int Ed Engl. 2021 Feb 23. doi: 10.1002/anie.202015422. PMID:33621416[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 | Balch M | Deng J | Matts R | Peng S
