Skip to main content
Journal cover image

Structural basis of multidrug recognition by BmrR, a transcription activator of a multidrug transporter.

Publication ,  Journal Article
Zheleznova, EE; Markham, PN; Neyfakh, AA; Brennan, RG
Published in: Cell
February 5, 1999

Multidrug-efflux transporters demonstrate an unusual ability to recognize multiple structurally dissimilar toxins. A comparable ability to bind diverse hydrophobic cationic drugs is characteristic of the Bacillus subtilis transcription regulator BmrR, which upon drug binding activates expression of the multidrug transporter Bmr. Crystal structures of the multidrug-binding domain of BmrR (2.7 A resolution) and of its complex with the drug tetraphenylphosphonium (2.8 A resolution) revealed a drug-induced unfolding and relocation of an alpha helix, which exposes an internal drug-binding pocket. Tetraphenylphosphonium binding is mediated by stacking and van der Waals contacts with multiple hydrophobic residues of the pocket and by an electrostatic interaction between the positively charged drug and a buried glutamate residue, which is the key to cation selectivity. Similar binding principles may be used by other multidrug-binding proteins.

Duke Scholars

Published In

Cell

DOI

ISSN

0092-8674

Publication Date

February 5, 1999

Volume

96

Issue

3

Start / End Page

353 / 362

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Trans-Activators
  • Rhodamines
  • Protein Conformation
  • Peptide Fragments
  • Models, Molecular
  • Ligands
  • Drug Resistance, Microbial
  • Dimerization
  • Developmental Biology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zheleznova, E. E., Markham, P. N., Neyfakh, A. A., & Brennan, R. G. (1999). Structural basis of multidrug recognition by BmrR, a transcription activator of a multidrug transporter. Cell, 96(3), 353–362. https://doi.org/10.1016/s0092-8674(00)80548-6
Zheleznova, E. E., P. N. Markham, A. A. Neyfakh, and R. G. Brennan. “Structural basis of multidrug recognition by BmrR, a transcription activator of a multidrug transporter.Cell 96, no. 3 (February 5, 1999): 353–62. https://doi.org/10.1016/s0092-8674(00)80548-6.
Zheleznova EE, Markham PN, Neyfakh AA, Brennan RG. Structural basis of multidrug recognition by BmrR, a transcription activator of a multidrug transporter. Cell. 1999 Feb 5;96(3):353–62.
Zheleznova, E. E., et al. “Structural basis of multidrug recognition by BmrR, a transcription activator of a multidrug transporter.Cell, vol. 96, no. 3, Feb. 1999, pp. 353–62. Pubmed, doi:10.1016/s0092-8674(00)80548-6.
Zheleznova EE, Markham PN, Neyfakh AA, Brennan RG. Structural basis of multidrug recognition by BmrR, a transcription activator of a multidrug transporter. Cell. 1999 Feb 5;96(3):353–362.
Journal cover image

Published In

Cell

DOI

ISSN

0092-8674

Publication Date

February 5, 1999

Volume

96

Issue

3

Start / End Page

353 / 362

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Trans-Activators
  • Rhodamines
  • Protein Conformation
  • Peptide Fragments
  • Models, Molecular
  • Ligands
  • Drug Resistance, Microbial
  • Dimerization
  • Developmental Biology