A unique peptide-based pharmacophore identifies an inhibitory compound against the A-subunit of Shiga toxin.

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-in

SUBMITTER: Watanabe-Takahashi M 

PROVIDER: S-EPMC9259562 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature