3p2h | pdb_00003p2h

Crystal structure of TofI in a ternary complex with an inhibitor and MTA

spinqualitylabelsall models 3p2h, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3p2h is a 1 chain structure with sequence from Burkholderia glumae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MTA, NOO Related: 3p2f Gene: tofI (Burkholderia glumae) Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Quorum sensing (QS) controls certain behaviors of bacteria in response to population density. In Gram-negative bacteria, QS is often mediated by N-acyl-l-homoserine lactones (acyl-HSLs). Because QS influences the virulence of many pathogenic bacteria, synthetic inhibitors of acyl-HSL synthases might be useful therapeutically for controlling pathogens. However, rational design of a potent QS antagonist has been thwarted by the lack of information concerning the binding interactions between acyl-HSL synthases and their ligands. In the Gram-negative bacterium Burkholderia glumae, QS controls virulence, motility, and protein secretion and is mediated by the binding of N-octanoyl-l-HSL (C8-HSL) to its cognate receptor, TofR. C8-HSL is synthesized by the acyl-HSL synthase TofI. In this study, we characterized two previously unknown QS inhibitors identified in a focused library of acyl-HSL analogs. Our functional and X-ray crystal structure analyses show that the first inhibitor, J8-C8, binds to TofI, occupying the binding site for the acyl chain of the TofI cognate substrate, acylated acyl-carrier protein. Moreover, the reaction byproduct, 5'-methylthioadenosine, independently binds to the binding site for a second substrate, S-adenosyl-l-methionine. Closer inspection of the mode of J8-C8 binding to TofI provides a likely molecular basis for the various substrate specificities of acyl-HSL synthases. The second inhibitor, E9C-3oxoC6, competitively inhibits C8-HSL binding to TofR. Our analysis of the binding of an inhibitor and a reaction byproduct to an acyl-HSL synthase may facilitate the design of a new class of QS-inhibiting therapeutic agents. Small-molecule inhibitor binding to an N-acyl-homoserine lactone synthase.,Chung J, Goo E, Yu S, Choi O, Lee J, Kim J, Kim H, Igarashi J, Suga H, Moon JS, Hwang I, Rhee S Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):12089-94. Epub 2011 Jul 5. PMID:21730159 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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