1R5X
JAMM: A Metalloprotease-like Zinc Site in the Proteasome and Signalosome
Summary for 1R5X
| Entry DOI | 10.2210/pdb1r5x/pdb |
| Descriptor | AfJAMM, ZINC ION (3 entities in total) |
| Functional Keywords | jamm, structural genomics, proteasome, signalosome, jab1, mpn, mov34, csn5, rpn11, unknown function |
| Biological source | Archaeoglobus fulgidus |
| Total number of polymer chains | 2 |
| Total formula weight | 30215.09 |
| Authors | Ambroggio, X.I.,Rees, D.C.,Deshaies, R.J. (deposition date: 2003-10-13, release date: 2003-11-25, Last modification date: 2024-02-14) |
| Primary citation | Ambroggio, X.I.,Rees, D.C.,Deshaies, R.J. JAMM: a metalloprotease-like zinc site in the proteasome and signalosome. Plos Biol., 2:E2-E2, 2004 Cited by PubMed 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. PubMed: 14737182DOI: 10.1371/journal.pbio.0020002 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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