Spotlight on the microbes that produce heat shock protein 90-targeting antibiotics

Piper, Peter and Millson, Stefan (2012) Spotlight on the microbes that produce heat shock protein 90-targeting antibiotics. Open Biology, 2 (DEC). ISSN 2046-2441

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Heat shock protein 90 (Hsp90) is a promising cancer drug target as a molecular chaperone critical for stabilization and activation of several of the oncoproteins that drive cancer progression. Its actions depend upon its essential ATPase, an activity fortuitously inhibited with a very high degree of selectivity by natural antibiotics: notably the actinomycete-derived benzoquinone ansamycins (e.g. geldanamycin) and certain fungal-derived resorcyclic acid lactones (e.g. radicicol). The molecular interactions made by these antibiotics when bound within the ADP/ATP-binding site of Hsp90 have served as templates for the development of several synthetic Hsp90 inhibitor drugs. Much attention now focuses on the clinical trials of these drugs. However, because microbes have evolved antibiotics to target Hsp90, it is probable that they often exploit Hsp90 inhibition when interacting with each other and with plants. Fungi known to produce Hsp90 inhibitors include mycoparasitic, as well as plant-pathogenic, endophytic and mycorrhizal species. The Hsp90 chaperone may, therefore, be a prominent target in establishing a number of mycoparasitic (interfungal), fungal pathogen–plant and symbiotic fungus–plant relationships. Furthermore the Hsp90 family proteins of the microbes that produce Hsp90 inhibitor antibiotics are able to reveal how drug resistance can arise by amino acid changes in the highly conserved ADP/ATP-binding site of Hsp90.

Keywords:Hsp90, molecular chaperone, benzoquinone ans amycins radicicol, drug resistance, fungal–plant interaction
Subjects:B Subjects allied to Medicine > B990 Subjects Allied to Medicine not elsewhere classified
C Biological Sciences > C700 Molecular Biology, Biophysics and Biochemistry
C Biological Sciences > C500 Microbiology
Divisions:College of Science > School of Life Sciences
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ID Code:15337
Deposited On:29 Oct 2014 21:31

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