| Literature DB >> 31011214 |
Wim Dejonghe1,2,3, Isha Sharma1,2, Bram Denoo4, Steven De Munck5,6, Qing Lu1,2, Kiril Mishev1,2,7, Haydar Bulut8, Evelien Mylle1,2, Riet De Rycke1,2,9, Mina Vasileva10, Daniel V Savatin1,2, Wim Nerinckx11,12, An Staes11,13, Andrzej Drozdzecki14,15, Dominique Audenaert14,15, Klaas Yperman1,2, Annemieke Madder4, Jiří Friml10, Daniël Van Damme1,2, Kris Gevaert11,13, Volker Haucke16, Savvas N Savvides5,6, Johan Winne4, Eugenia Russinova17,18.
Abstract
Clathrin-mediated endocytosis (CME) is a highly conserved and essential cellular process in eukaryotic cells, but its dynamic and vital nature makes it challenging to study using classical genetics tools. In contrast, although small molecules can acutely and reversibly perturb CME, the few chemical CME inhibitors that have been applied to plants are either ineffective or show undesirable side effects. Here, we identify the previously described endosidin9 (ES9) as an inhibitor of clathrin heavy chain (CHC) function in both Arabidopsis and human cells through affinity-based target isolation, in vitro binding studies and X-ray crystallography. Moreover, we present a chemically improved ES9 analog, ES9-17, which lacks the undesirable side effects of ES9 while retaining the ability to target CHC. ES9 and ES9-17 have expanded the chemical toolbox used to probe CHC function, and present chemical scaffolds for further design of more specific and potent CHC inhibitors across different systems.Entities:
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Year: 2019 PMID： 31011214 PMCID： PMC7612312 DOI： 10.1038/s41589-019-0262-1
Source DB: PubMed Journal: Nat Chem Biol ISSN： 1552-4450 Impact factor: 15.040