A Novel MFS-MDR Transporter, MdrP, Employs D223 as a Key Determinant in the Na⁺ Translocation Coupled to Norfloxacin Efflux.

ABSTRACT: Multidrug resistance (MDR) transporters of the major facilitator superfamily (MFS) were previously believed to drive the extrusion of multiple antimicrobial drugs through the coupling to proton translocation. Here, we present the identification of the first Na⁺-coupled MFS-MDR transporter, MdrP, which also can achieve H⁺-coupled drug efflux independently of Na⁺. Importantly, we propose that MdrP can extrude norfloxacin in a mode of drug/Na⁺ antiport, which has not yet been reported in any MFS member. On this basis, we further provide the insights into a novel Na⁺ and H⁺ coupling mechanism of MFS-MDR transporters, even for all secondary transporters. The most important finding lies in that D223 should mainly act as a key dete

SUBMITTER: Zhang R 

PROVIDER: S-EPMC7272687 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature