7VHD

Crystal structure of the STX2a complexed with R4A peptide

7VHD の概要

• エントリーDOI: 10.2210/pdb7vhd/pdb
• 分子名称: rRNA N-glycosylase, Shiga toxin 2 B subunit, ARG-ARG-ARG-ARG-ALA, ... (5 entities in total)
• 機能のキーワード: shiga toxin, toxin
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 73872.01

構造登録者

Senda, M.,Takahashi, M.,Nishikawa, K.,Senda, T. (登録日: 2021-09-22, 公開日: 2022-07-20, 最終更新日: 2024-10-16)

主引用文献

Watanabe-Takahashi, M.,Senda, M.,Yoshino, R.,Hibino, M.,Hama, S.,Terada, T.,Shimizu, K.,Senda, T.,Nishikawa, K.
A unique peptide-based pharmacophore identifies an inhibitory compound against the A-subunit of Shiga toxin.
Sci Rep, 12:11443-11443, 2022

PubMed Abstract: Shiga toxin (Stx), a major virulence factor of enterohemorrhagic Escherichia coli (EHEC), can cause fatal systemic complications. Recently, we identified a potent inhibitory peptide that binds to the catalytic A-subunit of Stx. Here, using biochemical structural analysis and X-ray crystallography, we determined a minimal essential peptide motif that occupies the catalytic cavity and is required for binding to the A-subunit of Stx2a, a highly virulent Stx subtype. Molecular dynamics simulations also identified the same motif and allowed determination of a unique pharmacophore for A-subunit binding. Notably, a series of synthetic peptides containing the motif efficiently inhibit Stx2a. In addition, pharmacophore screening and subsequent docking simulations ultimately identified nine Stx2a-interacting molecules out of a chemical compound database consisting of over 7,400,000 molecules. Critically, one of these molecules markedly inhibits Stx2a both in vitro and in vivo, clearly demonstrating the significance of the pharmacophore for identifying therapeutic agents against EHEC infection.

PubMed: 35794188
DOI: 10.1038/s41598-022-15316-1

実験手法

X-RAY DIFFRACTION (1.8 Å)