4URR

Tailspike protein of Sf6 bacteriophage bound to Shigella flexneri O- antigen octasaccharide fragment

4URR の概要

• エントリーDOI: 10.2210/pdb4urr/pdb
• 分子名称: BIFUNCTIONAL TAIL PROTEIN, alpha-L-rhamnopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-L-rhamnopyranose-(1-2)-alpha-L-rhamnopyranose-(1-3)-alpha-L-rhamnopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-L-rhamnopyranose-(1-2)-alpha-L-rhamnopyranose, MANGANESE (II) ION, ... (6 entities in total)
• 機能のキーワード: hydrolase, carbohydrate interaction, tailspike protein, beta helix
• 由来する生物種: SHIGELLA PHAGE SF6
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 338629.31

構造登録者

Gohlke, U.,Heinemann, U.,Seckler, R.,Barbirz, S. (登録日: 2014-07-01, 公開日: 2015-07-15, 最終更新日: 2024-01-10)

主引用文献

Kang, Y.,Gohlke, U.,Engstrom, O.,Hamark, C.,Scheidt, T.,Kunstmann, S.,Heinemann, U.,Widmalm, G.,Santer, M.,Barbirz, S.
Bacteriophage Tailspikes and Bacterial O-Antigens as a Model System to Study Weak-Affinity Protein-Polysaccharide Interactions.
J.Am.Chem.Soc., 138:9109-9118, 2016

PubMed Abstract: Understanding interactions of bacterial surface polysaccharides with receptor protein scaffolds is important for the development of antibiotic therapies. The corresponding protein recognition domains frequently form low-affinity complexes with polysaccharides that are difficult to address with experimental techniques due to the conformational flexibility of the polysaccharide. In this work, we studied the tailspike protein (TSP) of the bacteriophage Sf6. Sf6TSP binds and hydrolyzes the high-rhamnose, serotype Y O-antigen polysaccharide of the Gram-negative bacterium Shigella flexneri (S. flexneri) as a first step of bacteriophage infection. Spectroscopic analyses and enzymatic cleavage assays confirmed that Sf6TSP binds long stretches of this polysaccharide. Crystal structure analysis and saturation transfer difference (STD) NMR spectroscopy using an enhanced method to interpret the data permitted the detailed description of affinity contributions and flexibility in an Sf6TSP-octasaccharide complex. Dodecasaccharide fragments corresponding to three repeating units of the O-antigen in complex with Sf6TSP were studied computationally by molecular dynamics simulations. They showed that distortion away from the low-energy solution conformation found in the octasaccharide complex is necessary for ligand binding. This is in agreement with a weak-affinity functional polysaccharide-protein contact that facilitates correct placement and thus hydrolysis of the polysaccharide close to the catalytic residues. Our simulations stress that the flexibility of glycan epitopes together with a small number of specific protein contacts provide the driving force for Sf6TSP-polysaccharide complex formation in an overall weak-affinity interaction system.

PubMed: 27045683
DOI: 10.1021/jacs.6b00240

実験手法

X-RAY DIFFRACTION (1.95 Å)