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1r5x
From Proteopedia
JAMM: A Metalloprotease-like Zinc Site in the Proteasome and Signalosome
Overview
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.
About this Structure
1R5X is a Single protein structure of sequence from Archaeoglobus fulgidus dsm 4304. Full crystallographic information is available from OCA.
Reference
JAMM: a metalloprotease-like zinc site in the proteasome and signalosome., Ambroggio XI, Rees DC, Deshaies RJ, PLoS Biol. 2004 Jan;2(1):E2. Epub 2003 Nov 24. PMID:14737182 Page seeded by OCA on Sat May 3 07:07:18 2008
Categories: Archaeoglobus fulgidus dsm 4304 | Single protein | Ambroggio, X I. | Deshaies, R J. | Rees, D C. | Csn5 | Jab1 | Jamm | Mov34 | Mpn | Proteasome | Rpn11 | Signalosome | Structural genomic
