Most transport processes require input of energy - either in the form of ATP or membrane potential. When ATP is the source of energy, transport also requires the function of a dedicated ATPase. The molecular mechanisms of transport ATPases are poorly understood. It is not known how the energy is transduced to carry out transport, or what determines the polarity of transport. An intriguing question also concerns the substrate specificty of the transport proteins.
Most transporters are able to carry out transport of only one or a set of related substrates.
This system confers resistance to an anticancer drug doxorubicin in Streptomyces peucetius. Streptomyces is also the producer organism for this antibiotic. It has been hypothesized that resistance in this organism to its own antibiotic is the result of an efflux mechanism similar to the one employed by Pgp. Focus of this project is on understanding the biochemical mechanism of catalysis by the ATPase and how energy is transduced to allow opening and closing of the channel. To address questions related to interaction between subunits of the transporter, a variety of molecular and genetic techniques, including mutagenesis, suppressor analysis, and complementation are being used.