6dwc: Difference between revisions
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==Structure of the apo 4497 antibody Fab fragment== | |||
<StructureSection load='6dwc' size='340' side='right'caption='[[6dwc]], [[Resolution|resolution]] 2.27Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6dwc]] is a 4 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=6DWC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DWC FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.27Å</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></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=6dwc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dwc OCA], [https://pdbe.org/6dwc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dwc RCSB], [https://www.ebi.ac.uk/pdbsum/6dwc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dwc ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:30102105</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6dwc" style="background-color:#fffaf0;"></div> | ||
[[Category: Fong | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Fong R]] | |||
[[Category: Lupardus PJ]] | |||
Latest revision as of 09:14, 11 October 2023
Structure of the apo 4497 antibody Fab fragmentStructure of the apo 4497 antibody Fab fragment
Structural highlights
Publication Abstract from PubMedInfections 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. See AlsoReferences
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