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| | ==Immune evasion by a Staphylococcal Peroxidase Inhibitor that blocks myeloperoxidase== | | ==Immune evasion by a Staphylococcal Peroxidase Inhibitor that blocks myeloperoxidase== |
| - | <StructureSection load='5uzu' size='340' side='right' caption='[[5uzu]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='5uzu' size='340' side='right'caption='[[5uzu]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5uzu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UZU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UZU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5uzu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UZU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UZU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 2.403Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BN1321_100004, ERS072738_02531, ERS074020_02508, ERS140147_02483, HMPREF3211_00419 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885]), MPO ([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=5uzu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uzu OCA], [https://pdbe.org/5uzu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uzu RCSB], [https://www.ebi.ac.uk/pdbsum/5uzu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uzu ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Myeloperoxidase Myeloperoxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.2.2 1.11.2.2] </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=5uzu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uzu OCA], [http://pdbe.org/5uzu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uzu RCSB], [http://www.ebi.ac.uk/pdbsum/5uzu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uzu ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/PERM_HUMAN PERM_HUMAN]] Defects in MPO are the cause of myeloperoxidase deficiency (MPOD) [MIM:[http://omim.org/entry/254600 254600]]. A disorder characterized by decreased myeloperoxidase activity in neutrophils and monocytes that results in disseminated candidiasis.<ref>PMID:8142659</ref> <ref>PMID:7904599</ref> <ref>PMID:8621627</ref> <ref>PMID:9637725</ref> <ref>PMID:9354683</ref> | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PERM_HUMAN PERM_HUMAN]] Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of hypohalous acids, primarily hypochlorous acid in physiologic situations, and other toxic intermediates that greatly enhance PMN microbicidal activity. | + | [https://www.uniprot.org/uniprot/Q2G0X2_STAA8 Q2G0X2_STAA8] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5uzu" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5uzu" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Myeloperoxidase|Myeloperoxidase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Myeloperoxidase]] | + | [[Category: Large Structures]] |
| - | [[Category: Fevre, C]] | + | [[Category: Staphylococcus aureus]] |
| - | [[Category: Garcia, B]] | + | [[Category: Fevre C]] |
| - | [[Category: Geisbrecht, B V]] | + | [[Category: Garcia B]] |
| - | [[Category: Guerra, F]] | + | [[Category: Geisbrecht BV]] |
| - | [[Category: Haas, P]] | + | [[Category: Guerra F]] |
| - | [[Category: Jong, N de]]
| + | [[Category: Haas P]] |
| - | [[Category: Kessel, C van]]
| + | [[Category: Nijland R]] |
| - | [[Category: Nijland, R]] | + | [[Category: Ramyar K]] |
| - | [[Category: Ramyar, K]] | + | [[Category: Voyich-Kane J]] |
| - | [[Category: Strijp, J van]]
| + | [[Category: De Jong N]] |
| - | [[Category: Voyich-Kane, J]] | + | [[Category: Van Kessel C]] |
| - | [[Category: Oxidoreductase]] | + | [[Category: Van Strijp J]] |
| - | [[Category: Phagolysosome]] | + | |
| - | [[Category: Staphylococcal inhibitor innate immunity]] | + | |
| Structural highlights
5uzu is a 2 chain structure with sequence from Homo sapiens and Staphylococcus aureus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.403Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
Q2G0X2_STAA8
Publication Abstract from PubMed
Staphylococcus aureus is highly adapted to its host and has evolved many strategies to resist opsonization and phagocytosis. Even after uptake by neutrophils, S. aureus shows resistance to killing, which suggests the presence of phagosomal immune evasion molecules. With the aid of secretome phage display, we identified a highly conserved protein that specifically binds and inhibits human myeloperoxidase (MPO), a major player in the oxidative defense of neutrophils. We have named this protein "staphylococcal peroxidase inhibitor" (SPIN). To gain insight into inhibition of MPO by SPIN, we solved the cocrystal structure of SPIN bound to a recombinant form of human MPO at 2.4-A resolution. This structure reveals that SPIN acts as a molecular plug that prevents H2O2 substrate access to the MPO active site. In subsequent experiments, we observed that SPIN expression increases inside the neutrophil phagosome, where MPO is located, compared with outside the neutrophil. Moreover, bacteria with a deleted gene encoding SPIN showed decreased survival compared with WT bacteria after phagocytosis by neutrophils. Taken together, our results demonstrate that S. aureus secretes a unique proteinaceous MPO inhibitor to enhance survival by interfering with MPO-mediated killing.
Immune evasion by a staphylococcal inhibitor of myeloperoxidase.,de Jong NWM, Ramyar KX, Guerra FE, Nijland R, Fevre C, Voyich JM, McCarthy AJ, Garcia BL, van Kessel KPM, van Strijp JAG, Geisbrecht BV, Haas PA Proc Natl Acad Sci U S A. 2017 Aug 29;114(35):9439-9444. doi:, 10.1073/pnas.1707032114. Epub 2017 Aug 14. PMID:28808028[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ de Jong NWM, Ramyar KX, Guerra FE, Nijland R, Fevre C, Voyich JM, McCarthy AJ, Garcia BL, van Kessel KPM, van Strijp JAG, Geisbrecht BV, Haas PA. Immune evasion by a staphylococcal inhibitor of myeloperoxidase. Proc Natl Acad Sci U S A. 2017 Aug 29;114(35):9439-9444. doi:, 10.1073/pnas.1707032114. Epub 2017 Aug 14. PMID:28808028 doi:http://dx.doi.org/10.1073/pnas.1707032114
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