Mechanistic parallels in bacterial and human multidrug efflux transporters.
Bacteria carry a battery of multidrug transporters, which belong to six families of transporters. Members of at least three families the ATP-Binding Cassette superfamily, the Major Facilitator Superfamily and the Multidrug Endosomal Transporter family have been shown to contribute to multidrug resistance phenotype in eukaryotic cells. This review is focused on comparison of bacterial and eukaryotic transporters that do not have a common evolutionary trait and use different sources of energy to perform the transport. Yet they demonstrate an impressive resemblance. All multidrug transporters are capable of recognizing a broad spectrum of structurally diverse compounds. The accumulated data suggest that structural and mechanistic determinants of such ability are similar among unrelated proteins. Despite the apparent similarity, many features are still unique for different classes of transporters. Intriguingly, some cells appear to simultaneously express transporters belonging to different classes. Depending on mechanistic particularities of transporters such concurrent expression can result in synergistic or non-synergistic effects.
Zgurskaya
H I
HI
Department of Chemistry and Biochemistry, University of Oklahoma, 620 Parrington Oval RM 208, Norman, OK 73019, USA. hzgurskaya@chemdept.chem.ou.edu
Nikaido
H
H
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000737:chemistry / Q000378:metabolism*; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000378:metabolism; D001419:Bacteria / Q000378:metabolism; D001693:Biological Transport, Active; D004734:Energy Metabolism; D006801:Humans; D007700:Kinetics; D015394:Molecular Structure; D011485:Protein Binding
D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters