Substrate Specificity Checkpoints of the Multidrug Efflux Pump MexF from <i>Pseudomonas aeruginosa</i>.

ABSTRACT: Multidrug efflux pumps of the resistance-nodulation-division (RND) superfamily are major contributors to antibiotic resistance in Pseudomonas aeruginosa. Among these, the MexEF-OprN system, when overproduced in clinical isolates, confers resistance to fluoroquinolones, trimethoprim, and chloramphenicol. The inner-membrane RND transporter MexF in this complex exhibits a relatively narrow substrate specificity and the molecular mechanisms underlying this specificity are still unclear. Here, we employed a combination of experimental and computational approaches to dissect the role of a major putative recognition/binding site, the Access pocket, in the substrate specificity of MexF. Mutations at four selected positions D132, P136, G626, and S729 altered resistance profiles and substrate

SUBMITTER: Uddin MR 

PROVIDER: S-EPMC12910583 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature