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JAMM: A Metalloprotease-Like Zinc Site in the Proteasome and Signalosome

Open access
Ambroggio, Xavier I, Rees, Douglas C, Deshaies, Raymond J·2003·PLoS Biology

Abstract

The JAMM (JAB1/MPN/Mov34 metalloenzyme) motif in Rpn11 and Csn5 underlies isopeptidase activities intrinsic to the proteasome and signalosome, respectively. We show here that the archaebacterial protein AfJAMM possesses the key features of a zinc metalloprotease, yet with a distinct fold. The histidine and aspartic acid of the conserved EX(n)HS/THX(7)SXXD motif coordinate a zinc, whereas the glutamic acid hydrogen-bonds an aqua ligand. By analogy to the active site of thermolysin, we predict that the glutamic acid serves as an acid-base catalyst and the second serine stabilizes a tetrahedral intermediate. Mutagenesis of Csn5 confirms these residues are required for Nedd8 isopeptidase activity. The active site-like architecture specified by the JAMM motif motivates structure-based approaches to the study of JAMM domain proteins and the development of therapeutic proteasome and signalosome inhibitors.

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Metadata

Authors
Ambroggio, X. I., Rees, D. C., & Deshaies, R. J.
Venue
PLoS Biology
Published
2003-11-24
Volume
2
Issue
1
Pages
e2
ISSN
  • 1544-9173 (ISSN-L)
  • 1545-7885
OpenAlex
W2088504425
Cited by
247
References
1
FWCI
3.00
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: JAMM: A Metalloprotease-Like Zinc Site in the Proteasome and Signalosome. https://app.cochat.ai/papers/10.1371/journal.pbio.0020002
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Ambroggio, X. I., Rees, D. C., & Deshaies, R. J. (2003). JAMM: A Metalloprotease-Like Zinc Site in the Proteasome and Signalosome. PLoS Biology. https://doi.org/10.1371/journal.pbio.0020002

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