6dwc
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. References
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