The transmission interface of the Saccharomyces cerevisiae multidrug transporter Pdr5: Val-656 located in intracellular loop 2 plays a major role in drug resistance.

ABSTRACT: Pdr5 is a major ATP-binding cassette (ABC) multidrug transporter regarded as the founding member of a fungal subfamily of clinically significant efflux pumps. When these proteins are overexpressed, they confer broad-spectrum ultraresistance. To better understand the evolution of these proteins under selective pressure, we exposed a Saccharomyces cerevisiae yeast strain already overexpressing Pdr5 to a lethal concentration of cycloheximide. This approach gave mutations that confer greater resistance to a subset of transport substrates. One of these mutations, V656L, is located in intracellular loop 2 (ICL2), a region predicted by structural studies with several other ABC transporters to play a critical role in the transmission interface between the ATP hydrolysis and drug transport domains.

SUBMITTER: Downes MT 

PROVIDER: S-EPMC3553689 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature