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| | <StructureSection load='5ijt' size='340' side='right'caption='[[5ijt]], [[Resolution|resolution]] 2.15Å' scene=''> | | <StructureSection load='5ijt' size='340' side='right'caption='[[5ijt]], [[Resolution|resolution]] 2.15Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ijt]] is a 10 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=5IJT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IJT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ijt]] is a 10 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=5IJT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IJT 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]] 2.148Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRDX2, NKEFB, TDPX1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peroxiredoxin Peroxiredoxin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.1.15 1.11.1.15] </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=5ijt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ijt OCA], [https://pdbe.org/5ijt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ijt RCSB], [https://www.ebi.ac.uk/pdbsum/5ijt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ijt 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=5ijt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ijt OCA], [http://pdbe.org/5ijt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ijt RCSB], [http://www.ebi.ac.uk/pdbsum/5ijt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ijt ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PRDX2_HUMAN PRDX2_HUMAN]] Involved in redox regulation of the cell. Reduces peroxides with reducing equivalents provided through the thioredoxin system. It is not able to receive electrons from glutaredoxin. May play an important role in eliminating peroxides generated during metabolism. Might participate in the signaling cascades of growth factors and tumor necrosis factor-alpha by regulating the intracellular concentrations of H(2)O(2). | + | [https://www.uniprot.org/uniprot/PRDX2_HUMAN PRDX2_HUMAN] Involved in redox regulation of the cell. Reduces peroxides with reducing equivalents provided through the thioredoxin system. It is not able to receive electrons from glutaredoxin. May play an important role in eliminating peroxides generated during metabolism. Might participate in the signaling cascades of growth factors and tumor necrosis factor-alpha by regulating the intracellular concentrations of H(2)O(2). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Peroxiredoxin]]
| + | [[Category: Bolduc JA]] |
| - | [[Category: Bolduc, J A]] | + | [[Category: Haynes AC]] |
| - | [[Category: Haynes, A C]] | + | [[Category: Lowther WT]] |
| - | [[Category: Lowther, W T]] | + | |
| - | [[Category: Decamer disulfide bond]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
PRDX2_HUMAN Involved in redox regulation of the cell. Reduces peroxides with reducing equivalents provided through the thioredoxin system. It is not able to receive electrons from glutaredoxin. May play an important role in eliminating peroxides generated during metabolism. Might participate in the signaling cascades of growth factors and tumor necrosis factor-alpha by regulating the intracellular concentrations of H(2)O(2).
Publication Abstract from PubMed
2-Cys peroxiredoxins (Prxs) modulate hydrogen peroxide (H2O2)-mediated cell signaling. At high H2O2 levels, eukaryotic Prxs can be inactivated by hyperoxidation and are classified as sensitive Prxs. In contrast, prokaryotic Prxs are categorized as being resistant to hyperoxidation and lack the GGLG and C-terminal YF motifs present in the sensitive Prxs. Additional molecular determinants that account for the subtle differences in the susceptibility to hyperoxidation remain to be identified. A comparison of a new, 2.15-A-resolution crystal structure of Prx2 in the oxidized, disulfide-bonded state with the hyperoxidized structure of Prx2 and Prx1 in complex with sulfiredoxin revealed three structural regions that rearrange during catalysis. With these regions in hand, focused sequence analyses were performed comparing sensitive and resistant Prx groups. From this combinatorial approach, we discovered two novel hyperoxidation resistance motifs, motifs A and B, which were validated using mutagenesis of sensitive human Prxs and resistant Salmonella enterica serovar Typhimurium AhpC. Introduction and removal of these motifs, respectively, resulted in drastic changes in the sensitivity to hyperoxidation with Prx1 becoming 100-fold more resistant to hyperoxidation and AhpC becoming 800-fold more sensitive to hyperoxidation. The increased sensitivity of the latter AhpC variant was also confirmed in vivo These results support the function of motifs A and B as primary drivers for tuning the sensitivity of Prxs to different levels of H2O2, thus enabling the initiation of variable signaling or antioxidant responses in cells.
Novel hyperoxidation resistance motifs in 2-Cys peroxiredoxins.,Bolduc JA, Nelson KJ, Haynes AC, Lee J, Reisz JA, Graff AH, Clodfelter JE, Parsonage D, Poole LB, Furdui CM, Lowther WT J Biol Chem. 2018 Jul 27;293(30):11901-11912. doi: 10.1074/jbc.RA117.001690. Epub, 2018 Jun 8. PMID:29884768[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bolduc JA, Nelson KJ, Haynes AC, Lee J, Reisz JA, Graff AH, Clodfelter JE, Parsonage D, Poole LB, Furdui CM, Lowther WT. Novel hyperoxidation resistance motifs in 2-Cys peroxiredoxins. J Biol Chem. 2018 Jul 27;293(30):11901-11912. doi: 10.1074/jbc.RA117.001690. Epub, 2018 Jun 8. PMID:29884768 doi:http://dx.doi.org/10.1074/jbc.RA117.001690
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