Multidrug transporters from bacteria to man: similarities in structure and function

Abstract

Organisms ranging from bacteria to man possess transmembrane transporters which confer resistance to toxic compounds. Underlining their biological significance, prokaryotic and eukaryotic multidrug transport proteins are very similar in structure and function. Therefore, a study of the factors which determine the substrate specificity and energy coupling to drug translocation in 'simple' microorganisms has significance for multidrug resistance of mammalian cells. This chapter represents a comprehensive review in which we will summarize the current state of knowledge on three major aspects of drug efflux-based multidrug resistance: (i) the functional and structural similarities among secondary and ABC-type drug transporters encountered in prokaryotic and eukaryotic cells; (ii) the molecular mechanism of these transporters; and (iii) their potential physiological role.