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

نویسندگان

  • 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
چکیده

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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عنوان ژورنال:
  • Nature chemical biology

دوره 13 7  شماره 

صفحات  -

تاریخ انتشار 2017