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Department of Pharmacology

 
Author(s): 
van Veen, HW, Putman, M, Margolles, A, Sakamoto, K, Konings, WN
Abstract: 

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.

Publication ID: 
52886
Published date: 
March 2000
Publication source: 
pubmed
Publication type: 
Journal articles
Journal name: 
Pharmacol Ther
Publication volume: 
85
Publisher: 
Parent title: 
Edition: 
Publication number: