Molecular pharmacological characterization of two multidrug transporters in Lactococcus lactis.
The active extrusion of cytotoxic compounds from the cell by multidrug transporters is one of the major causes of failure of chemotherapeutic treatment of tumor cells and of infections by pathogenic microorganisms. A multidrug transporter in Lactococcus lactis, LmrA, is a member of the ATP-binding cassette superfamily and a bacterial homolog of the human multidrug resistance P-glycoprotein. Another multidrug transporter in Lactococcus lactis, LmrP, belongs to the major facilitator superfamily, and is one example of a rapidly expanding group of secondary multidrug transporters in microorganisms. Thus, LmrA and LmrP are transport proteins with very different protein structures, which use different mechanisms of energy coupling to transport drugs out of the cell. Surprisingly, both proteins have overlapping specificities for drugs, are inhibited by the same set of modulators, and transport drugs via a similar transport mechanism. The structure-function relationships that dictate drug recognition and transport by LmrP and LmrA represent an intriguing area of research.
van Veen
H W
HW
Department of Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Kerklaan 30, NL-9751 NN, Haren, The Netherlands. h.w.van.veen@biol.rug.nl
Putman
M
M
Margolles
A
A
Sakamoto
K
K
Konings
W N
WN
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000494:pharmacology*; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D001426:Bacterial Proteins; D001665:Binding Sites; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000378:metabolism*; D018432:Drug Resistance, Multiple / Q000502:physiology*; D013294:Lactococcus lactis / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D013329:Structure-Activity Relationship
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C101824:LmrA protein, Lactococcus lactis; C096807:LmrP protein, Lactococcus lactis