Qin Y, Dongchun N, Kowal J, Manolaridis I, Scott MJ, Stahlberg H and Locher K,Structures of ABCG2 under turnover conditions reveal a key step in the drug transport mechanism, Nature Commun. 2021, 12:4376.

ABCG2 is a multidrug transporter that affects drug pharmacokinetics and contributes to multidrug resistance of cancer cells. In this paper, the authors presented cryo-EM structures of ABCG2 under turnover conditions containing either the endogenous substrate estrone-3-sulfate or the exogenous substrate topotecan. The study revealed key conformational changes that are essential for substrate recognition and translocation, and allow ABCG2 to distinguish substrates from inhibitors.

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Bosshart PD, Kalbermatter D, Bonetti S, Fotiadis D, The making of a potent L-lactate transport inhibitor, Commun. Chem. 2021, 4:128

L-lactate is an important metabolite, energy source, and signalling molecule in health and disease. In this study, the authors reported the rational, structure-guided identification of potent, nanomolar affinity inhibitors acting on an L-lactate-specific SLC16 homologue from the bacterium Syntrophobacter fumaroxidans. In addition, they solved the high-resolution crystal structures of SfMCT with bound inhibitors, which provided important insights into the binding mechanism of these molecules on an atomic level.