| Literature DB >> 28459440 |
Linda Lauinger1, Jing Li2, Anton Shostak1, Ibrahim Avi Cemel1, Nati Ha1, Yaru Zhang2, Philipp E Merkl3, Simon Obermeyer3, Nicolas Stankovic-Valentin4, Tobias Schafmeier1, Walter J Wever5, Albert A Bowers5, Kyle P Carter6, Amy E Palmer6, Herbert Tschochner3, Frauke Melchior4, Raymond J Deshaies2,7, Michael Brunner1, Axel Diernfellner1.
Abstract
Thiolutin is a disulfide-containing antibiotic and anti-angiogenic compound produced by Streptomyces. Its biological targets are not known. We show that reduced thiolutin is a zinc chelator that inhibits the JAB1/MPN/Mov34 (JAMM) domain-containing metalloprotease Rpn11, a deubiquitinating enzyme of the 19S proteasome. Thiolutin also inhibits the JAMM metalloproteases Csn5, the deneddylase of the COP9 signalosome; AMSH, which regulates ubiquitin-dependent sorting of cell-surface receptors; and BRCC36, a K63-specific deubiquitinase of the BRCC36-containing isopeptidase complex and the BRCA1-BRCA2-containing complex. We provide evidence that other dithiolopyrrolones also function as inhibitors of JAMM metalloproteases.Entities:
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Year: 2017 PMID： 28459440 PMCID： PMC5792653 DOI： 10.1038/nchembio.2370
Source DB: PubMed Journal: Nat Chem Biol ISSN： 1552-4450 Impact factor: 15.040