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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="450" color="white" frame="true" align="right" spinBox="true"
caption="1r5x, resolution 2.30&Aring;" />
'''JAMM: A Metalloprotease-like Zinc Site in the Proteasome and Signalosome'''<br />


==Overview==
==JAMM: A Metalloprotease-like Zinc Site in the Proteasome and Signalosome==
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.
<StructureSection load='1r5x' size='340' side='right'caption='[[1r5x]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 
== Structural highlights ==
==About this Structure==
<table><tr><td colspan='2'>[[1r5x]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Archaeoglobus_fulgidus_DSM_4304 Archaeoglobus fulgidus DSM 4304]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R5X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1R5X FirstGlance]. <br>
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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1R5X OCA].  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
 
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
==Reference==
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1r5x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r5x OCA], [https://pdbe.org/1r5x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1r5x RCSB], [https://www.ebi.ac.uk/pdbsum/1r5x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1r5x ProSAT]</span></td></tr>
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14737182 14737182]
</table>
[[Category: Archaeoglobus fulgidus dsm 4304]]
== Function ==
[[Category: Single protein]]
[https://www.uniprot.org/uniprot/O28085_ARCFU O28085_ARCFU]  
[[Category: Ambroggio, X.I.]]
== Evolutionary Conservation ==
[[Category: Deshaies, R.J.]]
[[Image:Consurf_key_small.gif|200px|right]]
[[Category: Rees, D.C.]]
Check<jmol>
[[Category: ZN]]
  <jmolCheckbox>
[[Category: csn5]]
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r5/1r5x_consurf.spt"</scriptWhenChecked>
[[Category: jab1]]
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
[[Category: jamm]]
    <text>to colour the structure by Evolutionary Conservation</text>
[[Category: mov34]]
  </jmolCheckbox>
[[Category: mpn]]
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1r5x ConSurf].
[[Category: proteasome]]
<div style="clear:both"></div>
[[Category: rpn11]]
__TOC__
[[Category: signalosome]]
</StructureSection>
[[Category: structural genomics]]
[[Category: Archaeoglobus fulgidus DSM 4304]]
 
[[Category: Large Structures]]
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sat Nov 24 22:12:18 2007''
[[Category: Ambroggio XI]]
[[Category: Deshaies RJ]]
[[Category: Rees DC]]

Latest revision as of 08:20, 14 February 2024

JAMM: A Metalloprotease-like Zinc Site in the Proteasome and Signalosome

1r5x, resolution 2.30Å

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