Journal
FEBS LETTERS
Volume 580, Issue 22, Pages 5339-5343Publisher
WILEY
DOI: 10.1016/j.febslet.2006.09.005
Keywords
membrane protein; multidrug resistance; efflux pump
Funding
- Wellcome Trust Funding Source: Medline
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Bacterial multidrug efflux pumps operate by periplasmic recruitment and opening of TolC family outer membrane exit ducts by cognate inner membrane translocases. Directed evolution of active hybrid pumps was achieved by challenging a library of mutated, shuffled TolC variants to adapt to the noncognate Pseudomonas MexAB translocase, and confer resistance to the efflux substrate novobiocin. Amino acid substitutions in MexAB-adapted TolC variants that endowed high resistance were recreated independently, and revealed that MexAB-adaptation was conferred only by substitutions located in the lower a-helical barrel of TolC, specifically the periplasmic equatorial domain and entrance coiled coils. These changes converge to the native MexAB partner OprM, and indicate an interface key to the function and diversity of efflux pumps. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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