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Dynamic multidrug recognition by multidrug transcriptional repressor LmrR.

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  • معلومة اضافية
    • المصدر:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • الموضوع:
      Gene Expression Regulation, Bacterial*; Drug Resistance, Multiple, Bacterial/*genetics ; Lactococcus lactis/*genetics ; Multidrug Resistance-Associated Proteins/*chemistry ; Repressor Proteins/*chemistry; Base Sequence ; Benzimidazoles/chemistry ; Benzimidazoles/pharmacology ; Binding Sites ; Daunorubicin/chemistry ; Daunorubicin/pharmacology ; Ethidium/chemistry ; Ethidium/pharmacology ; Lactococcus lactis/drug effects ; Lactococcus lactis/metabolism ; Models, Molecular ; Molecular Sequence Data ; Multidrug Resistance-Associated Proteins/genetics ; Multidrug Resistance-Associated Proteins/metabolism ; Promoter Regions, Genetic ; Protein Binding ; Protein Conformation ; Repressor Proteins/genetics ; Repressor Proteins/metabolism ; Rhodamines/chemistry ; Rhodamines/pharmacology ; Transcription, Genetic
    • نبذة مختصرة :
      LmrR is a multidrug transcriptional repressor that controls the expression of a major multidrug transporter, LmrCD, in Lactococcus lactis. However, the molecular mechanism by which LmrR binds to structurally unrelated compounds and is released from the promoter region remains largely unknown. Here, we structurally and dynamically characterized LmrR in the apo, compound-bound and promoter-bound states. The compound-binding site of LmrR exhibits ps-μs dynamics in the apo state, and compound ligation shifts the preexisting conformational equilibrium to varying extents to achieve multidrug recognition. Meanwhile, the compound binding induces redistribution of ps-ns dynamics to the allosteric sites, which entropically favors the high-affinity recognition. Furthermore, the reciprocal compound/promoter binding by LmrR is achieved by the incompatible conformational ensembles between the compound- and promoter-bound states. Collectively, the data show how LmrR can dynamically exert its functions through promiscuous multi-target interactions, in a manner that cannot be understood by a static structural view.
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    • الرقم المعرف:
      0 (Benzimidazoles)
      0 (LmrC protein, Lactococcus lactis)
      0 (LmrD protein, Lactococcus lactis)
      0 (Multidrug Resistance-Associated Proteins)
      0 (Repressor Proteins)
      0 (Rhodamines)
      037VRW83CF (rhodamine 6G)
      EN464416SI (Ethidium)
      P976261J69 (bisbenzimide ethoxide trihydrochloride)
      ZS7284E0ZP (Daunorubicin)
    • الموضوع:
      Date Created: 20141119 Date Completed: 20151019 Latest Revision: 20181113
    • الموضوع:
      20240829
    • الرقم المعرف:
      PMC4235314
    • الرقم المعرف:
      10.1038/srep06922
    • الرقم المعرف:
      25403615