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| | ==Crystal structure of Human Glutaredoxin 2 complexed with glutathione== | | ==Crystal structure of Human Glutaredoxin 2 complexed with glutathione== |
| - | <StructureSection load='2fls' size='340' side='right' caption='[[2fls]], [[Resolution|resolution]] 2.05Å' scene=''> | + | <StructureSection load='2fls' size='340' side='right'caption='[[2fls]], [[Resolution|resolution]] 2.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2fls]] is a 1 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=2FLS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2FLS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2fls]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FLS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FLS FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GLRX2, GRX2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GLRX2, GRX2 ([https://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fls FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fls OCA], [http://pdbe.org/2fls PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2fls RCSB], [http://www.ebi.ac.uk/pdbsum/2fls PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2fls ProSAT]</span></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=2fls FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fls OCA], [https://pdbe.org/2fls PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fls RCSB], [https://www.ebi.ac.uk/pdbsum/2fls PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fls ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GLRX2_HUMAN GLRX2_HUMAN]] Glutathione-dependent oxidoreductase that facilitates the maintenance of mitochondrial redox homeostasis upon induction of apoptosis by oxidative stress. Involved in response to hydrogen peroxide and regulation of apoptosis caused by oxidative stress. Acts as a very efficient catalyst of monothiol reactions because of its high affinity for protein glutathione-mixed disulfides. Can receive electrons not only from glutathione (GSH), but also from thioredoxin reductase supporting both monothiol and dithiol reactions. Efficiently catalyzes both glutathionylation and deglutathionylation of mitochondrial complex I, which in turn regulates the superoxide production by the complex. Overexpression decreases the susceptibility to apoptosis and prevents loss of cardiolipin and cytochrome c release.<ref>PMID:11297543</ref> <ref>PMID:14676218</ref> <ref>PMID:15328416</ref> <ref>PMID:15649413</ref> | + | [[https://www.uniprot.org/uniprot/GLRX2_HUMAN GLRX2_HUMAN]] Glutathione-dependent oxidoreductase that facilitates the maintenance of mitochondrial redox homeostasis upon induction of apoptosis by oxidative stress. Involved in response to hydrogen peroxide and regulation of apoptosis caused by oxidative stress. Acts as a very efficient catalyst of monothiol reactions because of its high affinity for protein glutathione-mixed disulfides. Can receive electrons not only from glutathione (GSH), but also from thioredoxin reductase supporting both monothiol and dithiol reactions. Efficiently catalyzes both glutathionylation and deglutathionylation of mitochondrial complex I, which in turn regulates the superoxide production by the complex. Overexpression decreases the susceptibility to apoptosis and prevents loss of cardiolipin and cytochrome c release.<ref>PMID:11297543</ref> <ref>PMID:14676218</ref> <ref>PMID:15328416</ref> <ref>PMID:15649413</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Arrowsmith, C]] | | [[Category: Arrowsmith, C]] |
| | [[Category: Debreczeni, J]] | | [[Category: Debreczeni, J]] |
| Structural highlights
Function
[GLRX2_HUMAN] Glutathione-dependent oxidoreductase that facilitates the maintenance of mitochondrial redox homeostasis upon induction of apoptosis by oxidative stress. Involved in response to hydrogen peroxide and regulation of apoptosis caused by oxidative stress. Acts as a very efficient catalyst of monothiol reactions because of its high affinity for protein glutathione-mixed disulfides. Can receive electrons not only from glutathione (GSH), but also from thioredoxin reductase supporting both monothiol and dithiol reactions. Efficiently catalyzes both glutathionylation and deglutathionylation of mitochondrial complex I, which in turn regulates the superoxide production by the complex. Overexpression decreases the susceptibility to apoptosis and prevents loss of cardiolipin and cytochrome c release.[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.
References
- ↑ Lundberg M, Johansson C, Chandra J, Enoksson M, Jacobsson G, Ljung J, Johansson M, Holmgren A. Cloning and expression of a novel human glutaredoxin (Grx2) with mitochondrial and nuclear isoforms. J Biol Chem. 2001 Jul 13;276(28):26269-75. Epub 2001 Apr 10. PMID:11297543 doi:http://dx.doi.org/10.1074/jbc.M011605200
- ↑ Johansson C, Lillig CH, Holmgren A. Human mitochondrial glutaredoxin reduces S-glutathionylated proteins with high affinity accepting electrons from either glutathione or thioredoxin reductase. J Biol Chem. 2004 Feb 27;279(9):7537-43. Epub 2003 Dec 4. PMID:14676218 doi:http://dx.doi.org/10.1074/jbc.M312719200
- ↑ Lillig CH, Lonn ME, Enoksson M, Fernandes AP, Holmgren A. Short interfering RNA-mediated silencing of glutaredoxin 2 increases the sensitivity of HeLa cells toward doxorubicin and phenylarsine oxide. Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13227-32. Epub 2004 Aug 24. PMID:15328416 doi:http://dx.doi.org/10.1073/pnas.0401896101
- ↑ Enoksson M, Fernandes AP, Prast S, Lillig CH, Holmgren A, Orrenius S. Overexpression of glutaredoxin 2 attenuates apoptosis by preventing cytochrome c release. Biochem Biophys Res Commun. 2005 Feb 18;327(3):774-9. PMID:15649413 doi:http://dx.doi.org/10.1016/j.bbrc.2004.12.067
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