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| | ==Apo IsdH-NEAT3 in space group P3121 at a resolution of 1.85 A== | | ==Apo IsdH-NEAT3 in space group P3121 at a resolution of 1.85 A== |
| - | <StructureSection load='3vua' size='340' side='right' caption='[[3vua]], [[Resolution|resolution]] 1.85Å' scene=''> | + | <StructureSection load='3vua' size='340' side='right'caption='[[3vua]], [[Resolution|resolution]] 1.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3vua]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Staam Staam]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VUA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VUA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3vua]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_Mu50 Staphylococcus aureus subsp. aureus Mu50]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VUA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VUA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.85Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3quh|3quh]], [[3qug|3qug]], [[2z6f|2z6f]], [[2e7d|2e7d]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">harA, isdH, IsdH-NEAT3, sasI, SAV1731 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=158878 STAAM])</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=3vua FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vua OCA], [https://pdbe.org/3vua PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vua RCSB], [https://www.ebi.ac.uk/pdbsum/3vua PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vua 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=3vua FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vua OCA], [http://pdbe.org/3vua PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3vua RCSB], [http://www.ebi.ac.uk/pdbsum/3vua PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3vua ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ISDH_STAAM ISDH_STAAM]] Binds human plasma haptoglobin-hemoglobin complexes, haptoglobin and hemoglobin. Binds haptoglobin-hemoglobin complexes with significantly higher affinity than haptoglobin alone (By similarity). | + | [https://www.uniprot.org/uniprot/ISDH_STAAM ISDH_STAAM] Binds human plasma haptoglobin-hemoglobin complexes, haptoglobin and hemoglobin. Binds haptoglobin-hemoglobin complexes with significantly higher affinity than haptoglobin alone (By similarity). |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Antibiotic resistance is increasingly seen as a serious problem that threatens public health and erodes our capacity to effectively combat disease. So-called non-iron metalloporhyrins have shown promising antibacterial properties against a number of pathogenic bacteria including Staphylococcus aureus. However, little is known about the molecular mechanism(s) of action of these compounds and in particular how they reach the interior of the bacterial cells. A popular hypothesis indicates that non-iron metalloporphyrins infiltrate into bacterial cells like a "Trojan horse" using heme transport systems. Iron-regulated surface determinant (Isd) is the best characterized heme transport system of S. aureus. Herein we studied the molecular mechanism by which the extracellular heme-receptor IsdH-NEAT3 of Isd recognizes antimicrobial metalloporphyrins. We found that potent antibacterial porphyrins Ga(III)-protoporphyrin IX (PPIX) and Mn(III)-PPIX closely mimicked the properties of the natural ligand heme, namely (i) stable binding to IsdH-NEAT3 with comparable affinities for the receptor, (ii) nearly undistinghuishable three-dimensional structure when complexed with IsdH-NEAT3, and (iii) similar transfer properties to a second receptor IsdA. On the contrary, weaker antibacterial porphyrins Mg(II)-PPIX, Zn(II)-PPIX, and Cu(II)-PPIX were not captured effectively by IsdH-NEAT3 under our experimental conditions and displayed lower affinities. Moreover, reduction of Fe(III)-PPIX to Fe(II)-PPIX with dithionite abrogated stable binding to receptor. These data revealed a clear connection between oxidation state of metal and effective attachment to IsdH-NEAT3. Also, the strong correlation between binding affinity and reported antimicrobial potency suggested that the Isd system may be used by these antibacterial compounds to gain access to the interior of the cells. We hope these results will increase our understanding of Isd system of S. aureus and highlight its biomedical potential to deliver new and more efficient antibacterial treatments.
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| - | Molecular basis of recognition of antibacterial porphyrins by heme-transporter IsdH-NEAT3 of Staphylococcus aureus.,Moriwaki Y, Caaveiro JM, Tanaka Y, Tsutsumi H, Hamachi I, Tsumoto K Biochemistry. 2011 Aug 30;50(34):7311-20. Epub 2011 Aug 4. PMID:21797259<ref>PMID:21797259</ref>
| + | ==See Also== |
| - | | + | *[[Haptoglobin receptor|Haptoglobin receptor]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3vua" style="background-color:#fffaf0;"></div>
| + | |
| - | == References == | + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Staam]] | + | [[Category: Large Structures]] |
| - | [[Category: Caaveiro, J M.M]] | + | [[Category: Staphylococcus aureus subsp. aureus Mu50]] |
| - | [[Category: Moriwaki, Y]] | + | [[Category: Caaveiro JMM]] |
| - | [[Category: Tsumoto, K]] | + | [[Category: Moriwaki Y]] |
| - | [[Category: Vu, N T]] | + | [[Category: Tsumoto K]] |
| - | [[Category: Apo form]] | + | [[Category: Vu NT]] |
| - | [[Category: Cell wall]]
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| - | [[Category: Heme binding]]
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| - | [[Category: Heme transport]]
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| - | [[Category: Heme-binding protein]]
| + | |
| - | [[Category: Neat domain]]
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