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Thiolutin is a zinc chelator that inhibits the Rpn11 and other JAMM metalloproteases

Lauinger, Linda ; Li, Jing ; Shostak, Anton ; Cemel, Ibrahim Avi ; Ha, Nati ; Zhang, Yaru ; Merkl, Philipp E ; Obermeyer, Simon ; Stankovic-Valentin, Nicolas ; Schafmeier, Tobias ; Wever, Walter J ; Bowers, Albert A ; Carter, Kyle P ; Palmer, Amy E ; Tschochner, Herbert ; Melchior, Frauke ; Deshaies, Raymond J ; Brunner, Michael ; Diernfellner, Axel



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 ...

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