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| | ==HusA haemophore from Porphyromonas gingivalis== | | ==HusA haemophore from Porphyromonas gingivalis== |
| - | <StructureSection load='6bqs' size='340' side='right' caption='[[6bqs]], [[NMR_Ensembles_of_Models | 21 NMR models]]' scene=''> | + | <StructureSection load='6bqs' size='340' side='right'caption='[[6bqs]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6bqs]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Porgi Porgi]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BQS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BQS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6bqs]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Porphyromonas_gingivalis_W83 Porphyromonas gingivalis W83]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BQS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BQS FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6crl|6crl]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PG_2227 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=242619 PORGI])</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=6bqs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bqs OCA], [https://pdbe.org/6bqs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bqs RCSB], [https://www.ebi.ac.uk/pdbsum/6bqs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bqs 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=6bqs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bqs OCA], [http://pdbe.org/6bqs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bqs RCSB], [http://www.ebi.ac.uk/pdbsum/6bqs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bqs ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/Q7MSY3_PORGI Q7MSY3_PORGI] |
| - | Porphyromonas gingivalis is a keystone bacterial pathogen of chronic periodontitis. P. gingivalis is unable to synthesise the porphyrin macrocycle and relies on exogenous porphyrin, including haem or haem biosynthesis intermediates from host sources. We show that under the iron-limited conditions prevailing in tissue environments, P. gingivalis expresses a haemophore-like protein, HusA, to mediate the uptake of essential porphyrin and support pathogen survival within epithelial cells. The structure of HusA, together with titration studies, mutagenesis and in silico docking, show that haem binds in a hydrophobic groove on the alpha-helical structure without the typical iron coordination seen in other haemophores. This mode of interaction allows HusA to bind to a variety of abiotic and metal-free porphyrins with higher affinities than to haem. We exploit this unusual porphyrin-binding activity of HusA to target a prototypic deuteroporphyrin-metronidazole conjugate with restricted antimicrobial specificity in a Trojan horse strategy that effectively kills intracellular P. gingivalis.
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| - | Structural properties of a haemophore facilitate targeted elimination of the pathogen Porphyromonas gingivalis.,Gao JL, Kwan AH, Yammine A, Zhou X, Trewhella J, Hugrass BM, Collins DAT, Horne J, Ye P, Harty D, Nguyen KA, Gell DA, Hunter N Nat Commun. 2018 Oct 5;9(1):4097. doi: 10.1038/s41467-018-06470-0. PMID:30291238<ref>PMID:30291238</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 6bqs" style="background-color:#fffaf0;"></div>
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| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Porgi]] | + | [[Category: Large Structures]] |
| - | [[Category: Collins, D A.T]] | + | [[Category: Porphyromonas gingivalis W83]] |
| - | [[Category: Gell, D A]] | + | [[Category: Collins DAT]] |
| - | [[Category: Horne, J]] | + | [[Category: Gell DA]] |
| - | [[Category: Hugrass, B M]] | + | [[Category: Horne J]] |
| - | [[Category: Kwan, A H]] | + | [[Category: Hugrass BM]] |
| - | [[Category: Haem binding protein]] | + | [[Category: Kwan AH]] |
| - | [[Category: Heme binding protein]]
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