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| | <StructureSection load='6dw2' size='340' side='right'caption='[[6dw2]], [[Resolution|resolution]] 1.70Å' scene=''> | | <StructureSection load='6dw2' size='340' side='right'caption='[[6dw2]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6dw2]] is a 2 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=6DW2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6DW2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6dw2]] is a 2 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=6DW2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DW2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HD4:4-O-[2-acetamido-2-deoxy-beta-D-glucopyranosyl]-1-O-phosphono-D-ribitol'>HD4</scene>, <scene name='pdbligand=MLA:MALONIC+ACID'>MLA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 1.7Å</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=6dw2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dw2 OCA], [http://pdbe.org/6dw2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dw2 RCSB], [http://www.ebi.ac.uk/pdbsum/6dw2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dw2 ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HD4:4-O-[2-acetamido-2-deoxy-beta-D-glucopyranosyl]-1-O-phosphono-D-ribitol'>HD4</scene>, <scene name='pdbligand=MLA:MALONIC+ACID'>MLA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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=6dw2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dw2 OCA], [https://pdbe.org/6dw2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dw2 RCSB], [https://www.ebi.ac.uk/pdbsum/6dw2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dw2 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Fong, R]] | + | [[Category: Fong R]] |
| - | [[Category: Lupardus, P J]] | + | [[Category: Lupardus PJ]] |
| - | [[Category: Antibody]]
| + | |
| - | [[Category: Fab]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Staphylococcus aureus]]
| + | |
| - | [[Category: Wall teichoic acid]]
| + | |
| - | [[Category: Wta]]
| + | |
| Structural highlights
Publication Abstract from PubMed
Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a growing health threat worldwide. Efforts to identify novel antibodies that target S. aureus cell surface antigens are a promising direction in the development of antibiotics that can halt MRSA infection. We biochemically and structurally characterized three patient-derived MRSA-targeting antibodies that bind to wall teichoic acid (WTA), which is a polyanionic surface glycopolymer. In S. aureus, WTA exists in both alpha- and beta-forms, based on the stereochemistry of attachment of a N-acetylglucosamine residue to the repeating phosphoribitol sugar unit. We identified a panel of antibodies cloned from human patients that specifically recognize the alpha or beta form of WTA, and can bind with high affinity to pathogenic wild-type strains of S. aureus bacteria. To investigate how the beta-WTA specific antibodies interact with their target epitope, we determined the X-ray crystal structures of the three beta-WTA specific antibodies, 4462, 4497, and 6078 (Protein Data Bank IDs 6DWI, 6DWA, and 6DW2, respectively), bound to a synthetic WTA epitope. These structures reveal that all three of these antibodies, while utilizing distinct antibody complementarity-determining region sequences and conformations to interact with beta-WTA, fulfill two recognition principles: binding to the beta-GlcNAc pyranose core and triangulation of WTA phosphate residues with polar contacts. These studies reveal the molecular basis for targeting a unique S. aureus cell surface epitope and highlight the power of human patient-based antibody discovery techniques for finding novel pathogen-targeting therapeutics.
Structural investigation of human S. aureus-targeting antibodies that bind wall teichoic acid.,Fong R, Kajihara K, Chen M, Hotzel I, Mariathasan S, Hazenbos WLW, Lupardus PJ MAbs. 2018 Aug 13:1-13. doi: 10.1080/19420862.2018.1501252. PMID:30102105[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fong R, Kajihara K, Chen M, Hotzel I, Mariathasan S, Hazenbos WLW, Lupardus PJ. Structural investigation of human S. aureus-targeting antibodies that bind wall teichoic acid. MAbs. 2018 Aug 13:1-13. doi: 10.1080/19420862.2018.1501252. PMID:30102105 doi:http://dx.doi.org/10.1080/19420862.2018.1501252
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