Small-molecule inhibitor binding to an N-acyl-homoserine lactone synthase

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dc.contributor.authorJ Chung-
dc.contributor.authorE Goo-
dc.contributor.authorS Yu-
dc.contributor.authorO Choi-
dc.contributor.authorJ Lee-
dc.contributor.authorJ Kim-
dc.contributor.authorH Kim-
dc.contributor.authorJ Igarashi-
dc.contributor.authorH Suga-
dc.contributor.authorJae Sun Moon-
dc.contributor.authorI Hwang-
dc.contributor.authorS Rhee-
dc.date.accessioned2017-04-19T09:24:51Z-
dc.date.available2017-04-19T09:24:51Z-
dc.date.issued2011-
dc.identifier.issn0027-8424-
dc.identifier.uri10.1073/pnas.1103165108ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/10280-
dc.description.abstractQuorum 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.-
dc.publisherNatl Acad Sciences-
dc.titleSmall-molecule inhibitor binding to an N-acyl-homoserine lactone synthase-
dc.title.alternativeSmall-molecule inhibitor binding to an N-acyl-homoserine lactone synthase-
dc.typeArticle-
dc.citation.titleProceedings of National Academy of Sciences of United States of America-
dc.citation.number29-
dc.citation.endPage12094-
dc.citation.startPage12089-
dc.citation.volume108-
dc.contributor.affiliatedAuthorJae Sun Moon-
dc.contributor.alternativeName정지웅-
dc.contributor.alternativeName구은혜-
dc.contributor.alternativeName유상헌-
dc.contributor.alternativeName최옥희-
dc.contributor.alternativeName이지현-
dc.contributor.alternativeName김진우-
dc.contributor.alternativeName김홍섭-
dc.contributor.alternativeNameIgarashi-
dc.contributor.alternativeNameSuga-
dc.contributor.alternativeName문제선-
dc.contributor.alternativeName황인규-
dc.contributor.alternativeName이상기-
dc.identifier.bibliographicCitationProceedings of National Academy of Sciences of United States of America, vol. 108, no. 29, pp. 12089-12094-
dc.identifier.doi10.1073/pnas.1103165108-
dc.description.journalClassY-
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Division of Research on National Challenges > Plant Systems Engineering Research > 1. Journal Articles
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