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Crystal structure of the transcription activator BmrR bound to DNA and a drug.

Publication ,  Journal Article
Heldwein, EE; Brennan, RG
Published in: Nature
January 18, 2001

The efflux of chemically diverse drugs by multidrug transporters that span the membrane is one mechanism of multidrug resistance in bacteria. The concentrations of many of these transporters are controlled by transcription regulators, such as BmrR in Bacillus subtilis, EmrR in Escherichia coli and QacR in Staphylococcus aureus. These proteins promote transporter gene expression when they bind toxic compounds. BmrR activates transcription of the multidrug transporter gene, bmr, in response to cellular invasion by certain lipophilic cationic compounds (drugs). BmrR belongs to the MerR family, which regulates response to stress such as exposure to toxic compounds or oxygen radicals in bacteria. MerR proteins have homologous amino-terminal DNA-binding domains but different carboxy-terminal domains, which enable them to bind specific 'coactivator' molecules. When bound to coactivator, MerR proteins upregulate transcription by reconfiguring the 19-base-pair spacer found between the -35 and -10 promoter elements to allow productive interaction with RNA polymerase. Here we report the 3.0 A resolution structure of BmrR in complex with the drug tetraphenylphosphonium (TPP) and a 22-base-pair oligodeoxynucleotide encompassing the bmr promoter. The structure reveals an unexpected mechanism for transcription activation that involves localized base-pair breaking, and base sliding and realignment of the -35 and -10 operator elements.

Duke Scholars

Published In

Nature

DOI

ISSN

0028-0836

Publication Date

January 18, 2001

Volume

409

Issue

6818

Start / End Page

378 / 382

Location

England

Related Subject Headings

  • Transcriptional Activation
  • Trans-Activators
  • Recombinant Proteins
  • Protein Conformation
  • Protein Binding
  • Promoter Regions, Genetic
  • Organophosphorus Compounds
  • Onium Compounds
  • Nucleic Acid Conformation
  • Models, Molecular
 

Citation

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Heldwein, E. E., & Brennan, R. G. (2001). Crystal structure of the transcription activator BmrR bound to DNA and a drug. Nature, 409(6818), 378–382. https://doi.org/10.1038/35053138
Heldwein, E. E., and R. G. Brennan. “Crystal structure of the transcription activator BmrR bound to DNA and a drug.Nature 409, no. 6818 (January 18, 2001): 378–82. https://doi.org/10.1038/35053138.
Heldwein EE, Brennan RG. Crystal structure of the transcription activator BmrR bound to DNA and a drug. Nature. 2001 Jan 18;409(6818):378–82.
Heldwein, E. E., and R. G. Brennan. “Crystal structure of the transcription activator BmrR bound to DNA and a drug.Nature, vol. 409, no. 6818, Jan. 2001, pp. 378–82. Pubmed, doi:10.1038/35053138.
Heldwein EE, Brennan RG. Crystal structure of the transcription activator BmrR bound to DNA and a drug. Nature. 2001 Jan 18;409(6818):378–382.
Journal cover image

Published In

Nature

DOI

ISSN

0028-0836

Publication Date

January 18, 2001

Volume

409

Issue

6818

Start / End Page

378 / 382

Location

England

Related Subject Headings

  • Transcriptional Activation
  • Trans-Activators
  • Recombinant Proteins
  • Protein Conformation
  • Protein Binding
  • Promoter Regions, Genetic
  • Organophosphorus Compounds
  • Onium Compounds
  • Nucleic Acid Conformation
  • Models, Molecular