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==Structural Dissection of a Gating Mechanism Preventing Misactivation of Ubiquitin by NEDD8's E1 (APPBP1-UBA3Arg190Ala-NEDD8Ala72Arg)==
==Structural Dissection of a Gating Mechanism Preventing Misactivation of Ubiquitin by NEDD8's E1 (APPBP1-UBA3Arg190Ala-NEDD8Ala72Arg)==
<StructureSection load='3dbh' size='340' side='right' caption='[[3dbh]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
<StructureSection load='3dbh' size='340' side='right'caption='[[3dbh]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3dbh]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DBH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3DBH FirstGlance]. <br>
<table><tr><td colspan='2'>[[3dbh]] 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=3DBH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DBH FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.85&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1r4m|1r4m]], [[1r4n|1r4n]], [[1yov|1yov]], [[3dbl|3dbl]], [[3dbr|3dbr]]</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>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NAE1, APPBP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), UBA3, UBE1C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), NEDD8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3dbh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dbh OCA], [https://pdbe.org/3dbh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dbh RCSB], [https://www.ebi.ac.uk/pdbsum/3dbh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dbh ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3dbh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dbh OCA], [http://pdbe.org/3dbh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3dbh RCSB], [http://www.ebi.ac.uk/pdbsum/3dbh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3dbh ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://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> [[http://www.uniprot.org/uniprot/NEDD8_HUMAN NEDD8_HUMAN]] Ubiquitin-like protein which plays an important role in cell cycle control and embryogenesis. Covalent attachment to its substrates requires prior activation by the E1 complex UBE1C-APPBP1 and linkage to the E2 enzyme UBE2M. Attachment of NEDD8 to cullins activates their associated E3 ubiquitin ligase activity, and thus promotes polyubiquitination and proteasomal degradation of cyclins and other regulatory proteins.<ref>PMID:10318914</ref> <ref>PMID:10597293</ref> <ref>PMID:11953428</ref>  [[http://www.uniprot.org/uniprot/UBA3_HUMAN UBA3_HUMAN]] Catalytic 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. Down-regulates steroid receptor activity. Necessary for cell cycle progression.<ref>PMID:10207026</ref> <ref>PMID:9694792</ref> <ref>PMID:12740388</ref> 
[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>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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==See Also==
==See Also==
*[[NEDD8|NEDD8]]
*[[NEDD8|NEDD8]]
*[[Ubiquitin activating enzyme|Ubiquitin activating enzyme]]
*[[3D structures of Ubiquitin activating enzyme|3D structures of Ubiquitin activating enzyme]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Schulman, B A]]
[[Category: Large Structures]]
[[Category: Souphron, J]]
[[Category: Schulman BA]]
[[Category: Activating enzyme]]
[[Category: Souphron J]]
[[Category: Apoptosis]]
[[Category: Atp-binding]]
[[Category: Cell cycle]]
[[Category: Ligase]]
[[Category: Membrane]]
[[Category: Nucleotide-binding]]
[[Category: Nucleus]]
[[Category: Polymorphism]]
[[Category: Ubl conjugation pathway]]

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