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| | <StructureSection load='6e8l' size='340' side='right'caption='[[6e8l]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='6e8l' size='340' side='right'caption='[[6e8l]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6e8l]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Strp2 Strp2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E8L OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6E8L FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6e8l]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae_D39 Streptococcus pneumoniae D39]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E8L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6E8L FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SPD_0373 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=373153 STRP2])</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]] 2.3Å</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=6e8l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e8l OCA], [https://pdbe.org/6e8l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6e8l RCSB], [https://www.ebi.ac.uk/pdbsum/6e8l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6e8l ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6e8l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e8l OCA], [http://pdbe.org/6e8l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e8l RCSB], [http://www.ebi.ac.uk/pdbsum/6e8l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e8l ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/A0A0H2ZNM1_STRP2 A0A0H2ZNM1_STRP2]] Antioxidant protein with alkyl hydroperoxidase activity. Required for the reduction of the AhpC active site cysteine residues and for the regeneration of the AhpC enzyme activity.[SAAS:SAAS00088543] | + | [https://www.uniprot.org/uniprot/A0A0H2ZNM1_STRP2 A0A0H2ZNM1_STRP2] Antioxidant protein with alkyl hydroperoxidase activity. Required for the reduction of the AhpC active site cysteine residues and for the regeneration of the AhpC enzyme activity.[SAAS:SAAS00088543] |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | During aerobic growth, the Gram-positive facultative anaerobe and opportunistic human pathogen Streptococcus pneumoniae generates large amounts of hydrogen peroxide that can accumulate to millimolar concentrations. The mechanism by which this catalase-negative bacterium can withstand endogenous hydrogen peroxide is incompletely understood. The enzyme alkylhydroperoxidase D (AhpD) has been shown to contribute to pneumococcal virulence and oxidative stress responses in vivo We demonstrate here that SpAhpD exhibits weak thiol-dependent peroxidase activity and, unlike the previously reported Mycobacterium tuberculosis AhpC/D system, SpAhpD does not mediate electron transfer to SpAhpC. A 2.3-A resolution crystal structure revealed several unusual structural features, including a three-cysteine active site architecture that is buried in a deep pocket, in contrast to the two-cysteine active site found in other AhpD enzymes. All single-cysteine SpAhpD variants remained partially active, and LC-MS/MS analyses revealed that the third cysteine, Cys-163, formed disulfide bonds with either of two cysteines in the canonical Cys-78-X-X-Cys-81 motif. We observed that SpAhpD formed a dimeric quaternary structure both in the crystal and in solution, and that the highly conserved Asn-76 of the AhpD core motif is important for SpAhpD folding. In summary, SpAhpD is a weak peroxidase and does not transfer electrons to AhpC, and therefore does not fit existing models of bacterial AhpD antioxidant defense mechanisms. We propose that it is unlikely that SpAhpD removes peroxides either directly or via AhpC, and that SpAhpD cysteine oxidation may act as a redox switch or mediate electron transfer with other thiol proteins.
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| - | | + | |
| - | Structure-function analyses of alkylhydroperoxidase D from Streptococcus pneumoniae reveal an unusual three-cysteine active site architecture.,Meng Y, Sheen CR, Magon NJ, Hampton MB, Dobson RCJ J Biol Chem. 2020 Mar 6;295(10):2984-2999. doi: 10.1074/jbc.RA119.012226. Epub, 2020 Jan 23. PMID:31974167<ref>PMID:31974167</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6e8l" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Peroxiredoxin]] | + | [[Category: Streptococcus pneumoniae D39]] |
| - | [[Category: Strp2]]
| + | [[Category: Coombes D]] |
| - | [[Category: Coombes, D]] | + | [[Category: Davies J]] |
| - | [[Category: Davies, J]] | + | [[Category: Dobson R]] |
| - | [[Category: Dobson, R]] | + | [[Category: Hampton M]] |
| - | [[Category: Hampton, M]] | + | [[Category: Horne C]] |
| - | [[Category: Horne, C]] | + | [[Category: Meng Y]] |
| - | [[Category: Meng, Y]] | + | [[Category: North R]] |
| - | [[Category: North, R]] | + | |
| - | [[Category: Alkylhydroperoxidase peroxiredoxin]]
| + | |
| - | [[Category: Oxidoreductase]]
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