AcrB - The Multisite Drug Efflux Transporter

Amanda Chin & Ananth Kumar

  • Preface
  • Structure
  • Functional Mechanism
  • Experiments
  • Summary
  • References

References

Article
Nakashima R. et al. Structures of the multidrug exporter AcrB reveal a proximal multisite drug-binding pocket. Nature. 480, 565-570 (2011).

 
Additional Sources
1. Murakami, S., Nakashima, R., Yamashita, E. & Yamaguchi, A. Crystal structure of bacterial multidrug efflux transporter AcrB. Nature 419, 587–593 (2002).

2. Murakami, S., Nakashima, R., Yamashita, E., Matsumoto, T. & Yamaguchi, A. Crystal structures of a multidrug transporter reveal a functionally rotating mechanism. Nature 443, 173–179 (2006).

3. Okusu, H., Ma, D. & Nikaido, H. AcrAB efflux pump plays a major role in the antibiotic resistance phenotype of Escherichia coli multiple-antibiotic-resistance (Mar) mutants. J. Bacteriol. 178, 306–308 (1996)

4. Sulavik, M. C. et al. Antibiotic susceptibility profiles of Escherichia coli strains lacking multidrug efflux pump genes. Antimicrob. Agents Chemother. 45, 1126–1136 (2001)

5. Ma, D., Cook, D. N., Hearst, J. E. & Nikaido, H. Efflux pumps and drug resistance in Gram-negative bacteria. Trends Microbiol. 2, 489–493 (1994)

6. Poole, K., Krebes, K., McNally, C. & Neshat, S. Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon. J. Bacteriol. 175, 7363–7372 (1993)
Email ThisBlogThis!Share to XShare to FacebookShare to Pinterest

No comments:

Post a Comment

Home
Subscribe to: Posts (Atom)

Overview

Gram-negative bacteria exhibit higher intrinsic levels of resistance to a range of drugs as compared to the Gram-positive strain. This enhanced tolerance is attributed to multidrug efflux pumps embedded in cell membranes which recognize a wide variety of substrates. These transporters are tripartite and associate with periplasmic proteins to form complexes responsible for the efflux of drugs out of the cell directly to the external surroundings.

Our blog is concentrated on a particular transporter called AcrB, which associates with AcrA and TolC. The primary focus is the mechanism utilized by AcrB to transport both high and low molecular weight drugs. Crystal structures of the protein have revealed and provided evidence that the presence of an additional binding site facilitates the mechanism. Results from site-directed mutagenesis have contributed affirmation toward the proposed mechanism.

Structural, mechanistic and experimental details relevant to the transport mechanism by AcrB are presented on our blog. We hope that the information provided will be insightful and contribute toward you understanding of the function of AcrB.

Contributors

  • Amanda
  • Ananth

Blog Archive

  • ▼  2012 (1)
    • ▼  May (1)
      • Preface
Ethereal theme. Theme images by neomistyle. Powered by Blogger.