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| | ==The crystal structure of G4, the poxviral disulfide oxidoreductase essential for cytoplasmic disulfide bond formation== | | ==The crystal structure of G4, the poxviral disulfide oxidoreductase essential for cytoplasmic disulfide bond formation== |
| - | <StructureSection load='2g2q' size='340' side='right' caption='[[2g2q]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='2g2q' size='340' side='right'caption='[[2g2q]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2g2q]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Vaccinia_virus Vaccinia virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2G2Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2G2Q FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2g2q]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Vaccinia_virus Vaccinia virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2G2Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2G2Q FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.5Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">g4l ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10245 Vaccinia virus])</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=2g2q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2g2q OCA], [https://pdbe.org/2g2q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2g2q RCSB], [https://www.ebi.ac.uk/pdbsum/2g2q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2g2q 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=2g2q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2g2q OCA], [http://pdbe.org/2g2q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2g2q RCSB], [http://www.ebi.ac.uk/pdbsum/2g2q PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GLRX2_VACCW GLRX2_VACCW]] Glutaredoxin necessary for virion morphogenesis and virus replication. Functions as a thiol-disulfide transfer protein between membrane-associated A2.5 and substrates L1 or F9. The complete pathway for formation of disulfide bonds in intracellular virion membrane proteins sequentially involves oxidation of E10, A2.5 and G4. Exhibit thioltransferase and dehydroascorbate reductase activities in vitro.<ref>PMID:10982364</ref> <ref>PMID:11752136</ref> <ref>PMID:11983854</ref> <ref>PMID:8955061</ref> | + | [https://www.uniprot.org/uniprot/GLRX2_VACCW GLRX2_VACCW] Glutaredoxin necessary for virion morphogenesis and virus replication. Functions as a thiol-disulfide transfer protein between membrane-associated A2.5 and substrates L1 or F9. The complete pathway for formation of disulfide bonds in intracellular virion membrane proteins sequentially involves oxidation of E10, A2.5 and G4. Exhibit thioltransferase and dehydroascorbate reductase activities in vitro.<ref>PMID:10982364</ref> <ref>PMID:11752136</ref> <ref>PMID:11983854</ref> <ref>PMID:8955061</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/g2/2g2q_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/g2/2g2q_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Vaccinia virus]] | | [[Category: Vaccinia virus]] |
| - | [[Category: Garboczi, D N]] | + | [[Category: Garboczi DN]] |
| - | [[Category: Lin, D Y]] | + | [[Category: Lin DY]] |
| - | [[Category: Su, H P]] | + | [[Category: Su HP]] |
| - | [[Category: G4]]
| + | |
| - | [[Category: Orthopox]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Poxvirus]]
| + | |
| - | [[Category: Thioredoxin-fold]]
| + | |
| Structural highlights
Function
GLRX2_VACCW Glutaredoxin necessary for virion morphogenesis and virus replication. Functions as a thiol-disulfide transfer protein between membrane-associated A2.5 and substrates L1 or F9. The complete pathway for formation of disulfide bonds in intracellular virion membrane proteins sequentially involves oxidation of E10, A2.5 and G4. Exhibit thioltransferase and dehydroascorbate reductase activities in vitro.[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The possibility of the release of smallpox virus into a predominantly nonimmunized population highlights the importance of understanding poxvirus biology. Poxviruses encode a conserved pathway that is required to oxidize disulfide bonds in nascent viral proteins that fold in the reducing environment of the eukaryotic host cytoplasm. We present the structure of the last enzyme of the vaccinia virus pathway, G4, which is almost identical in smallpox virus. G4 catalyzes the formation of disulfide bonds in proteins that are critical for virus maturation and host cell infection. G4 contains a thioredoxin fold and a Cys-X-X-Cys active site. In solution, G4 monomers and dimers are observed. In the crystal, G4 is found as a dimer that buries 4,500 A(2) in the interface and occludes the active site, which could protect the reactive disulfide from reduction in the cytoplasm. The structure serves as a model for drug design targeting viral disulfide bond formation.
The structure of G4, the poxvirus disulfide oxidoreductase essential for virus maturation and infectivity.,Su HP, Lin DY, Garboczi DN J Virol. 2006 Aug;80(15):7706-13. PMID:16840349[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ White CL, Weisberg AS, Moss B. A glutaredoxin, encoded by the G4L gene of vaccinia virus, is essential for virion morphogenesis. J Virol. 2000 Oct;74(19):9175-83. PMID:10982364
- ↑ White CL, Senkevich TG, Moss B. Vaccinia virus G4L glutaredoxin is an essential intermediate of a cytoplasmic disulfide bond pathway required for virion assembly. J Virol. 2002 Jan;76(2):467-72. PMID:11752136
- ↑ Senkevich TG, White CL, Koonin EV, Moss B. Complete pathway for protein disulfide bond formation encoded by poxviruses. Proc Natl Acad Sci U S A. 2002 May 14;99(10):6667-72. Epub 2002 Apr 30. PMID:11983854 doi:http://dx.doi.org/10.1073/pnas.062163799
- ↑ Gvakharia BO, Koonin EK, Mathews CK. Vaccinia virus G4L gene encodes a second glutaredoxin. Virology. 1996 Dec 15;226(2):408-11. PMID:8955061 doi:http://dx.doi.org/10.1006/viro.1996.0669
- ↑ Su HP, Lin DY, Garboczi DN. The structure of G4, the poxvirus disulfide oxidoreductase essential for virus maturation and infectivity. J Virol. 2006 Aug;80(15):7706-13. PMID:16840349 doi:80/15/7706
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