2fqt
From Proteopedia
Crystal structure of B.subtilis LuxS in complex with (2S)-2-Amino-4-[(2R,3S)-2,3-dihydroxy-3-N-hydroxycarbamoyl-propylmercapto]butyric acid
Overview
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.
About this Structure
2FQT is a Single protein structure of sequence from Bacillus subtilis. Full crystallographic information is available from OCA.
Reference
Design and synthesis of substrate and intermediate analogue inhibitors of S-ribosylhomocysteinase., Shen G, Rajan R, Zhu J, Bell CE, Pei D, J Med Chem. 2006 May 18;49(10):3003-11. PMID:16686542 Page seeded by OCA on Sun May 4 04:12:33 2008
