Promiscuity in multidrug recognition and transport: the bacterial MFS Mdr transporters.
Multidrug (Mdr) transport is an obstacle to the successful treatment of cancer and infectious diseases, and it is mediated by Mdr transporters that recognize and export an unusually broad spectrum of chemically dissimilar toxic compounds. Therefore, in addition to its clinical significance, the Mdr transport phenomenon presents intriguing and challenging mechanistic queries. Recent studies of secondary Mdr transporters of the major facilitator superfamily (MFS) have revealed that they are promiscuous not only regarding their substrate recognition profile, but also with respect to matters of energy utilization, electrical and chemical flexibility in the Mdr recognition pocket, and surprisingly, also in their physiological functions.
Lewinson
Oded
O
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, 76100, Israel.
Adler
Julia
J
Sigal
Nadejda
N
Bibi
Eitan
E
D000595:Amino Acid Sequence; D001665:Binding Sites; D001692:Biological Transport; D029968:Escherichia coli Proteins / Q000378:metabolism; D019450:Genes, MDR; D019563:Mechanics; D026901:Membrane Transport Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011522:Protons; D055672:Static Electricity
D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011522:Protons; C118438:Mdfa protein, E coli