Evolution and Function of the Multidrug Resistance-linked ABC Transporters in Bacteria and Cancer Cells
Zuben E. Sauna and Suresh V. Ambudkar
from: ABC Transporters in Microorganisms: Research, Innovation and Value as Targets against Drug Resistance (Edited by: Alicia Ponte-Sucre). Caister Academic Press, U.K. (2009)
The ATP-binding cassette (ABC) genes constitute one of the largest super-families in living organisms. The majority of ABC proteins encode membrane proteins that utilize the energy of ATP binding and hydrolysis to transport a diverse set of compounds. ABC systems are critical to the cellular physiology of prokaryotes, facilitating the import of nutrients, the extrusion of toxins and for DNA repair. In eukaryotes, ABC proteins function primarily as efflux pumps (or as import pumps in intracellular organelles) playing important roles in protecting organisms from xenobiotics, antigen presentation, cholesterol and lipid transport. As ABC transporters extrude an unusually large set of chemically diverse compounds, they impede the treatment of microbial infections and human cancers and are implicated in multidrug resistance (MDR). Among prokaryotes, ABC proteins segregate into 29 families belonging to three main classes approximating the functional divisions of the ABC system (importers, exporters and "other"). However, the vertebrate ABC proteins do not have the functional or organizational diversity of the prokaryotic proteins. The primary focus of this review is to discuss the evolution and structure-function relationship of microbial and mammalian ABC transporters responsible for MDR and the current status of substrate specificity and mechanistic aspects of mammalian ABC drug transporters read more ...