Identification of an allosteric pocket on human Hsp70 reveals a mode of inhibition of this therapeutically important protein Journal Article
| Authors: | Rodina, A.; Patel, P. D.; Kang, Y.; Patel, Y.; Baaklini, I.; Wong, M. J. H.; Taldone, T.; Yan, P.; Yang, C.; Maharaj, R.; Gozman, A.; Patel, M. R.; Patel, H. J.; Chirico, W.; Erdjument-Bromage, H.; Talele, T. T.; Young, J. C.; Chiosis, G. |
| Article Title: | Identification of an allosteric pocket on human Hsp70 reveals a mode of inhibition of this therapeutically important protein |
| Abstract: | Summary Hsp70s are important cancer chaperones that act upstream of Hsp90 and exhibit independent anti-apoptotic activities. To develop chemical tools for the study of human Hsp70, we developed a homology model that unveils a previously unknown allosteric site located in the nucleotide binding domain of Hsp70. Combining structure-based design and phenotypic testing, we discovered a previously unknown inhibitor of this site, YK5. In cancer cells, this compound is a potent and selective binder of the cytosolic but not the organellar human Hsp70s and has biological activity partly by interfering with the formation of active oncogenic Hsp70/Hsp90/client protein complexes. YK5 is a small molecule inhibitor rationally designed to interact with an allosteric pocket of Hsp70 and represents a previously unknown chemical tool to investigate cellular mechanisms associated with Hsp70. © 2013 Elsevier Ltd. |
| Journal Title: | Chemistry and Biology |
| Volume: | 20 |
| Issue: | 12 |
| ISSN: | 1074-5521 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2013-12-19 |
| Start Page: | 1469 |
| End Page: | 1480 |
| Language: | English |
| DOI: | 10.1016/j.chembiol.2013.10.008 |
| PROVIDER: | scopus |
| PMCID: | PMC3985611 |
| PUBMED: | 24239008 |
| DOI/URL: | |
| Notes: | Export Date: 3 February 2014 -- CODEN: CBOLE -- Source: Scopus |
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