1r5x

Publication Abstract from PubMed

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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.