1r5x
From Proteopedia
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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 with ZN as ligand. 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 Nov 24 22:12:18 2007
Categories: Archaeoglobus fulgidus dsm 4304 | Single protein | Ambroggio, X.I. | Deshaies, R.J. | Rees, D.C. | ZN | Csn5 | Jab1 | Jamm | Mov34 | Mpn | Proteasome | Rpn11 | Signalosome | Structural genomics
