Thiolutin is a zinc chelator that inhibits the Rpn11 and other JAMM metalloproteases
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...
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| Main Authors: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
01 May 2017
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| In: |
Nature chemical biology
Year: 2017, Volume: 13, Issue: 7, Pages: 709-714 |
| ISSN: | 1552-4469 |
| DOI: | 10.1038/nchembio.2370 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1038/nchembio.2370 Verlag, Volltext: https://www.nature.com/articles/nchembio.2370 
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| Author Notes: | Linda Lauinger, Jing Li, Anton Shostak, Ibrahim Avi Cemel, Nati Ha, Yaru Zhang, Philipp E. Merkl, Simon Obermeyer, Nicolas Stankovic-Valentin, Tobias Schafmeier, Walter J. Wever, Albert A. Bowers, Kyle P. Carter, Amy E. Palmer, Herbert Tschochner, Frauke Melchior, Raymond J. Deshaies, Michael Brunner & Axel Diernfellner |
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| 520 | |a 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. | ||
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