2FQO

Crystal structure of B. subtilis LuxS in complex with (2S)-2-Amino-4-[(2R,3R)-2,3-dihydroxy-3-N- hydroxycarbamoyl-propylmercapto]butyric acid

2FQO の概要

• エントリーDOI: 10.2210/pdb2fqo/pdb
• 関連するPDBエントリー: 2FQT
• 分子名称: S-ribosylhomocysteine lyase, COBALT (II) ION, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: luxs, quorum sensing, lyase
• 由来する生物種: Bacillus subtilis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18161.51

構造登録者

Shen, G.,Rajan, R.,Zhu, J.,Bell, C.E.,Pei, D. (登録日: 2006-01-18, 公開日: 2006-05-30, 最終更新日: 2023-08-30)

主引用文献

Shen, G.,Rajan, R.,Zhu, J.,Bell, C.E.,Pei, D.
Design and Synthesis of Substrate and Intermediate Analogue Inhibitors of S-Ribosylhomocysteinase
J.Med.Chem., 49:3003-3011, 2006

PubMed Abstract: S-Ribosylhomocysteinase (LuxS) catalyzes the cleavage of the thioether linkage in S-ribosylhomocysteine (SRH) to produce homocysteine and 4,5-dihydroxy-2,3-pentanedione, the precursor of autoinducer 2. Inhibitors of LuxS should interfere with bacterial interspecies communication and potentially provide a novel class of antibacterial agents. LuxS utilizes a divalent metal ion as a Lewis acid during catalysis. In this work, a series of structural analogues of the substrate SRH and a 2-ketone intermediate were designed and synthesized. Kinetic studies indicate that the compounds act as reversible, competitive inhibitors against LuxS, with the most potent inhibitors having K(I) values in the submicromolar range. These represent the most potent LuxS inhibitors that have been reported to date. Cocrystal structures of LuxS bound with two of the inhibitors largely confirmed the design principles, i.e., the importance of both the homocysteine and ribose moieties in high-affinity binding to the LuxS active site.

PubMed: 16686542
DOI: 10.1021/jm060047g

実験手法

X-RAY DIFFRACTION (1.87 Å)