1r5x: Difference between revisions
New page: left|200px<br /><applet load="1r5x" size="450" color="white" frame="true" align="right" spinBox="true" caption="1r5x, resolution 2.30Å" /> '''JAMM: A Metalloprote... |
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[[Image:1r5x.gif|left|200px]]<br /><applet load="1r5x" size=" | [[Image:1r5x.gif|left|200px]]<br /><applet load="1r5x" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1r5x, resolution 2.30Å" /> | caption="1r5x, resolution 2.30Å" /> | ||
'''JAMM: A Metalloprotease-like Zinc Site in the Proteasome and Signalosome'''<br /> | '''JAMM: A Metalloprotease-like Zinc Site in the Proteasome and Signalosome'''<br /> | ||
==Overview== | ==Overview== | ||
The JAMM (JAB1/MPN/Mov34 metalloenzyme) motif in Rpn11 and Csn5 underlies | 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== | ==About this Structure== | ||
1R5X is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Archaeoglobus_fulgidus_dsm_4304 Archaeoglobus fulgidus dsm 4304] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 1R5X is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Archaeoglobus_fulgidus_dsm_4304 Archaeoglobus fulgidus dsm 4304] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R5X OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Archaeoglobus fulgidus dsm 4304]] | [[Category: Archaeoglobus fulgidus dsm 4304]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Ambroggio, X | [[Category: Ambroggio, X I.]] | ||
[[Category: Deshaies, R | [[Category: Deshaies, R J.]] | ||
[[Category: Rees, D | [[Category: Rees, D C.]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
[[Category: csn5]] | [[Category: csn5]] | ||
| Line 27: | Line 27: | ||
[[Category: structural genomics]] | [[Category: structural genomics]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:47:31 2008'' | ||
Revision as of 12:47, 21 February 2008
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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
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