Structure of an engineered multidrug transporter MdfA reveals the molecular basis for substrate recognition.

ABSTRACT: MdfA is a prototypical H⁺-coupled multidrug transporter that is characterized by extraordinarily broad substrate specificity. The involvement of specific H-bonds in MdfA-drug interactions and the simplicity of altering the substrate specificity of MdfA contradict the promiscuous nature of multidrug recognition, presenting a baffling conundrum. Here we show the X-ray structures of MdfA variant I239T/G354E in complexes with three electrically different ligands, determined at resolutions up to 2.2 Å. Our structures reveal that I239T/G354E interacts with these compounds differently from MdfA and that I239T/G354E possesses two discrete, non-overlapping substrate-binding sites. Our results shed new light on the molecular design of multidrug-binding and protonation sites and highlight

SUBMITTER: Wu HH 

PROVIDER: S-EPMC6572762 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature