8GCW

Stx2A1(Y77A)-P6 peptide

8GCW の概要

• エントリーDOI: 10.2210/pdb8gcw/pdb
• 分子名称: rRNA N-glycosylase, P stalk protein (3 entities in total)
• 機能のキーワード: toxin
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28519.00

構造登録者

Rudolph, M.J.,Li, X.P. (登録日: 2023-03-03, 公開日: 2024-03-06, 最終更新日: 2024-09-18)

主引用文献

Rudolph, M.J.,Tsymbal, A.M.,Dutta, A.,Davis, S.A.,Algava, B.,Roberge, J.Y.,Tumer, N.E.,Li, X.P.
Fragment Screening to Identify Inhibitors Targeting Ribosome Binding of Shiga Toxin 2.
Acs Infect Dis., 10:2814-2825, 2024

PubMed Abstract: Shiga toxins are the main virulence factors of Shiga toxin producing (STEC) and . There is no effective therapy to counter the disease caused by these toxins. The A1 subunits of Shiga toxins bind the C-termini of ribosomal P-stalk proteins to depurinate the sarcin/ricin loop. The ribosome binding site of Shiga toxin 2 has not been targeted by small molecules. We screened a fragment library against the A1 subunit of Shiga toxin 2 (Stx2A1) and identified a fragment, , which bound at the ribosome binding site and mimicked the binding mode of the P-stalk proteins. We synthesized analogs of and identified a series of molecules with similar affinity and inhibitory activity. These are the first compounds that bind at the ribosome binding site of Stx2A1 and inhibit activity. These compounds hold great promise for further inhibitor development against STEC infection.

PubMed: 38873918
DOI: 10.1021/acsinfecdis.4c00224

実験手法

X-RAY DIFFRACTION (3.1 Å)