2nvu

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[[Image:2nvu.png|left|200px]]
 
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{{STRUCTURE_2nvu| PDB=2nvu | SCENE= }}
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==Structure of APPBP1-UBA3~NEDD8-NEDD8-MgATP-Ubc12(C111A), a trapped ubiquitin-like protein activation complex==
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<StructureSection load='2nvu' size='340' side='right'caption='[[2nvu]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2nvu]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NVU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NVU FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2nvu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nvu OCA], [https://pdbe.org/2nvu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nvu RCSB], [https://www.ebi.ac.uk/pdbsum/2nvu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nvu ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/ULA1_HUMAN ULA1_HUMAN] Regulatory subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Necessary for cell cycle progression through the S-M checkpoint. Overexpression of NAE1 causes apoptosis through deregulation of NEDD8 conjugation.<ref>PMID:10207026</ref> <ref>PMID:10722740</ref> <ref>PMID:12740388</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nv/2nvu_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2nvu ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Ubiquitin-like proteins (UBLs) are conjugated by dynamic E1-E2-E3 enzyme cascades. E1 enzymes activate UBLs by catalysing UBL carboxy-terminal adenylation, forming a covalent E1 throught UBL thioester intermediate, and generating a thioester-linked E2 throught UBL product, which must be released for subsequent reactions. Here we report the structural analysis of a trapped UBL activation complex for the human NEDD8 pathway, containing NEDD8's heterodimeric E1 (APPBP1-UBA3), two NEDD8s (one thioester-linked to E1, one noncovalently associated for adenylation), a catalytically inactive E2 (Ubc12), and MgATP. The results suggest that a thioester switch toggles E1-E2 affinities. Two E2 binding sites depend on NEDD8 being thioester-linked to E1. One is unmasked by a striking E1 conformational change. The other comes directly from the thioester-bound NEDD8. After NEDD8 transfer to E2, reversion to an alternate E1 conformation would facilitate release of the E2 throught NEDD8 thioester product. Thus, transferring the UBL's thioester linkage between successive conjugation enzymes can induce conformational changes and alter interaction networks to drive consecutive steps in UBL cascades.
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===Structure of APPBP1-UBA3~NEDD8-NEDD8-MgATP-Ubc12(C111A), a trapped ubiquitin-like protein activation complex===
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Basis for a ubiquitin-like protein thioester switch toggling E1-E2 affinity.,Huang DT, Hunt HW, Zhuang M, Ohi MD, Holton JM, Schulman BA Nature. 2007 Jan 25;445(7126):394-8. Epub 2007 Jan 14. PMID:17220875<ref>PMID:17220875</ref>
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{{ABSTRACT_PUBMED_17220875}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==About this Structure==
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<div class="pdbe-citations 2nvu" style="background-color:#fffaf0;"></div>
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[[2nvu]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NVU OCA].
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==See Also==
==See Also==
*[[NEDD8|NEDD8]]
*[[NEDD8|NEDD8]]
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*[[3D structures of Ubiquitin activating enzyme|3D structures of Ubiquitin activating enzyme]]
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==Reference==
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*[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]]
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<ref group="xtra">PMID:017220875</ref><references group="xtra"/>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Holton, J M.]]
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[[Category: Large Structures]]
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[[Category: Huang, D T.]]
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[[Category: Holton JM]]
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[[Category: Hunt, H W.]]
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[[Category: Huang DT]]
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[[Category: Ohi, M D.]]
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[[Category: Hunt HW]]
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[[Category: Schulman, B A.]]
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[[Category: Ohi MD]]
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[[Category: Zhuang, M.]]
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[[Category: Schulman BA]]
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[[Category: Adenylation]]
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[[Category: Zhuang M]]
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[[Category: Conformational change]]
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[[Category: E1]]
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[[Category: E2]]
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[[Category: Ligase]]
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[[Category: Multifunction macromolecular complex]]
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[[Category: Nedd8]]
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[[Category: Protein turnover]]
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[[Category: Switch]]
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[[Category: Thioester]]
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[[Category: Ubiquitin]]
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Current revision

Structure of APPBP1-UBA3~NEDD8-NEDD8-MgATP-Ubc12(C111A), a trapped ubiquitin-like protein activation complex

PDB ID 2nvu

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