JAMM: A Metalloprotease-Like Zinc Site in the Proteasome and Signalosome
CaltechAUTHORS
View Archive Info| Field | Value | |
| Title |
JAMM: A Metalloprotease-Like Zinc Site in the Proteasome and Signalosome
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| Creator |
Ambroggio, Xavier I.
Rees, Douglas C. Deshaies, Raymond J. |
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| Subject |
Caltech Library Services
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| Description |
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 EXnHS/THX7SXXD 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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| Publisher |
Public Library of Science
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| Date |
2004-01
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://authors.library.caltech.edu/261/1/AMBpb04.pdf
Ambroggio, Xavier I. and Rees, Douglas C. and Deshaies, Raymond J. (2004) JAMM: A Metalloprotease-Like Zinc Site in the Proteasome and Signalosome. PLoS Biology, 2 (1). pp. 113-119. ISSN 1544-9173. PMCID PMC300881. http://resolver.caltech.edu/CaltechAUTHORS:AMBpb04 <http://resolver.caltech.edu/CaltechAUTHORS:AMBpb04> |
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| Relation |
http://resolver.caltech.edu/CaltechAUTHORS:AMBpb04
http://authors.library.caltech.edu/261/ |
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