9JXT

An aldehyde-containing intermediate of SufS in complex with (2R,3R)-3-ethoxycarbonylaziridine-2-carboxylic acid

これはPDB形式変換不可エントリーです。

9JXT の概要

• エントリーDOI: 10.2210/pdb9jxt/pdb
• 分子名称: Cysteine desulfurase SufS, DI(HYDROXYETHYL)ETHER, (2~{S})-2-[(~{E})-[2-methyl-3-oxidanyl-5-(phosphonooxymethyl)pyridin-4-yl]methylideneamino]-3-oxidanylidene-propanoic acid, ... (4 entities in total)
• 機能のキーワード: cysteine desulfurase, biosynthetic protein
• 由来する生物種: Bacillus subtilis subsp. subtilis str. 168
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 47024.91

構造登録者

Nakamura, R.,Fujishiro, T. (登録日: 2024-10-11, 公開日: 2025-07-16, 最終更新日: 2025-09-03)

主引用文献

Fujishiro, T.,Otsuka, H.,Nakamura, R.,Fujihara, T.
Discovery of an Aziridine-Based Inhibitor That Targets Cysteine Desulfurase Type II SufS via High-Throughput X‐ray Crystallography.
Acs Med.Chem.Lett., 16:1546-1553, 2025

PubMed Abstract: Structure-based drug design is an emerging technology for developing new drugs. However, in silico modeling and predicting inhibitors covalently bound to cofactor-containing enzymes remain challenging. Here, we demonstrate an alternative approach for visualizing protein inhibitor binding via X-ray crystallography of PLP-dependent enzyme crystals. Specifically, we used crystals of type II cysteine desulfurase, SufS, a drug-target enzyme in the iron-sulfur cluster biosynthetic SUF system. We identified (2,3)-3-ethoxycarbonylaziridine-2-carboxylic acid (EAC) as a selective inhibitor of SufS. The X-ray crystal structures of SufS soaked with EAC for 12 and 24 h showed PLP-ligand conjugates. Two PLP-ligand conjugate species were assigned to l-α-formylglycine-PLP external aldimine and aminomalonate-PLP external aldimine, which could be caused by the aziridine ring opening reaction, removal of the ethyl ester, and air oxidation. This strategy could help identify new drug candidates specific to SufS, a new drug target in pathogenic microorganisms containing iron-sulfur cluster biosynthetic SUF systems.

PubMed: 40832543
DOI: 10.1021/acsmedchemlett.5c00168

実験手法

X-RAY DIFFRACTION (2.2 Å)