Bedaquiline inhibits the yeast and human mitochondrial ATP synthases.

Bedaquiline (BDQ, Sirturo) has been approved to treat multidrug resistant forms of Mycobacterium tuberculosis. Prior studies suggested that BDQ was a selective inhibitor of the ATP synthase from M. tuberculosis.

Structure and mechanism of a redesigned multidrug transporter from the Major Facilitator Superfamily.

The rapid increase of multidrug resistance poses urgent threats to human health. Multidrug transporters prompt multidrug resistance by exporting different therapeutics across cell membranes, often by utilizing the H electrochemical gradient. MdfA from Escherichia coli is a prototypical H -dependent multidrug transporter belonging to the Major Facilitator Superfamily.

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

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.

High-resolution cryo-EM analysis of the yeast ATP synthase in a lipid membrane.

Mitochondrial adenosine triphosphate (ATP) synthase comprises a membrane embedded F motor that rotates to drive ATP synthesis in the F subunit. We used single-particle cryo-electron microscopy (cryo-EM) to obtain structures of the full complex in a lipid bilayer in the absence or presence of the inhibitor oligomycin at 3.6- and 3.

Structure and function of the divalent anion/Na symporter from Vibrio cholerae and a humanized variant.

Integral membrane proteins of the divalent anion/Na symporter (DASS) family translocate dicarboxylate, tricarboxylate or sulphate across cell membranes, typically by utilizing the preexisting Na gradient. The molecular determinants for substrate recognition by DASS remain obscure, largely owing to the absence of any substrate-bound DASS structure. Here we present 2.