6DWA

Structure of the 4497 Antibody Fab fragment bound to a Staphylococcus aureus wall techoic acid analog

6DWA の概要

• エントリーDOI: 10.2210/pdb6dwa/pdb
• 関連するPDBエントリー: 6DW2
• 分子名称: 4497 Fab Light Chain, 4497 Fab Heavy Chain, 4-O-[2-acetamido-2-deoxy-beta-D-glucopyranosyl]-1-O-phosphono-D-ribitol, ... (4 entities in total)
• 機能のキーワード: antibody, fab, wall teichoic acid, wta, staphylococcus aureus, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 105353.76

構造登録者

Fong, R.,Lupardus, P.J. (登録日: 2018-06-26, 公開日: 2018-08-29, 最終更新日: 2024-11-06)

主引用文献

Fong, R.,Kajihara, K.,Chen, M.,Hotzel, I.,Mariathasan, S.,Hazenbos, W.L.W.,Lupardus, P.J.
Structural investigation of human S. aureus-targeting antibodies that bind wall teichoic acid.
MAbs, 10:979-991, 2018

PubMed Abstract: 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 α- and β-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 α or β form of WTA, and can bind with high affinity to pathogenic wild-type strains of S. aureus bacteria. To investigate how the β-WTA specific antibodies interact with their target epitope, we determined the X-ray crystal structures of the three β-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 β-WTA, fulfill two recognition principles: binding to the β-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.

PubMed: 30102105
DOI: 10.1080/19420862.2018.1501252

実験手法

X-RAY DIFFRACTION (1.922 Å)