Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedS-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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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