1r4m

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[[Image:1r4m.png|left|200px]]
 
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{{STRUCTURE_1r4m| PDB=1r4m | SCENE= }}
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==APPBP1-UBA3-NEDD8, an E1-ubiquitin-like protein complex==
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<StructureSection load='1r4m' size='340' side='right'caption='[[1r4m]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1r4m]] is a 12 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=1R4M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1R4M 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]] 3&#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=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=1r4m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r4m OCA], [https://pdbe.org/1r4m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1r4m RCSB], [https://www.ebi.ac.uk/pdbsum/1r4m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1r4m 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/r4/1r4m_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=1r4m 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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E1 enzymes initiate ubiquitin-like protein (ubl) transfer cascades by catalyzing adenylation of the ubl's C terminus. An E1's selectivity for its cognate ubl is essential because the E1 subsequently coordinates the ubl with its correct downstream pathway. We report here the structure of the 120 kDa quaternary complex between human APPBP1-UBA3, a heterodimeric E1, its ubl NEDD8, and ATP. The E1 selectively recruits NEDD8 through a bipartite interface, involving a domain common to all ubl activating enzymes including bacterial ancestors, and also eukaryotic E1-specific sequences. By modeling ubiquitin into the NEDD8 binding site and performing mutational analysis, we identify a single conserved arginine in APPBP1-UBA3 that acts as a selectivity gate, preventing misactivation of ubiquitin by NEDD8's E1. NEDD8 residues that interact with E1 correspond to residues in ubiquitin important for binding the proteasome and other ubiquitin-interacting proteins, suggesting that the conjugation and recognition machineries have coevolved for each specific ubl.
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===APPBP1-UBA3-NEDD8, an E1-ubiquitin-like protein complex===
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The structure of the APPBP1-UBA3-NEDD8-ATP complex reveals the basis for selective ubiquitin-like protein activation by an E1.,Walden H, Podgorski MS, Huang DT, Miller DW, Howard RJ, Minor DL Jr, Holton JM, Schulman BA Mol Cell. 2003 Dec;12(6):1427-37. PMID:14690597<ref>PMID:14690597</ref>
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{{ABSTRACT_PUBMED_14690597}}
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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 1r4m" style="background-color:#fffaf0;"></div>
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[[1r4m]] is a 12 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=1R4M 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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== References ==
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<ref group="xtra">PMID:014690597</ref><references group="xtra"/>
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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: Podgorski, M S.]]
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[[Category: Holton JM]]
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[[Category: Schulman, B A.]]
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[[Category: Podgorski MS]]
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[[Category: Walden, H.]]
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[[Category: Schulman BA]]
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[[Category: Cell cycle]]
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[[Category: Walden H]]

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APPBP1-UBA3-NEDD8, an E1-ubiquitin-like protein complex

PDB ID 1r4m

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