2FQT
Crystal structure of B.subtilis LuxS in complex with (2S)-2-Amino-4-[(2R,3S)-2,3-dihydroxy-3-N-hydroxycarbamoyl-propylmercapto]butyric acid
Summary for 2FQT
Entry DOI | 10.2210/pdb2fqt/pdb |
Related | 2FQO |
Descriptor | S-ribosylhomocysteine lyase, SULFATE ION, COBALT (II) ION, ... (5 entities in total) |
Functional Keywords | luxs, quorum sensing, lyase |
Biological source | Bacillus subtilis |
Total number of polymer chains | 1 |
Total formula weight | 18257.58 |
Authors | Shen, G.,Rajan, R.,Zhu, J.,Bell, C.E.,Pei, D. (deposition date: 2006-01-18, release date: 2006-05-30, Last modification date: 2023-08-30) |
Primary citation | Shen, G.,Rajan, R.,Zhu, J.,Bell, C.E.,Pei, D. Design and Synthesis of Substrate Analogue Inhibitors of S-Ribosylhomocysteinase (LuxS) J.Med.Chem., 49:3003-3011, 2006 Cited by 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: 16686542DOI: 10.1021/jm060047g PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.79 Å) |
Structure validation
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