Fig. 1: Cryo-EM structure of Oat1 bound to α-KG.
From: Molecular basis for selective uptake and elimination of organic anions in the kidney by OAT1
a, OAT1 exchanges α-KG, produced from the tricarboxylic acid (TCA) cycle or transported into the cell via NaDC3, for organic anions and drugs. The transport function of OAT1 is inhibited by the drug probenecid and enhanced by chloride binding. b, Cryo-EM structure of Oat1 showing the extracellular and intracellular domains and the position of the substrate α-KG and the chloride ion. c, Top-down view of Oat1 highlighting the binding sites for α-KG (site 1) and chloride (site 2), respectively. d, Zoomed-in view of site 1, showing the main interactions formed with α-KG. Key residues interacting with the substrate are shown as sticks and hydrogen bonds are represented as dashed lines. Cryo-EM density for the ligand is shown (purple and threshold 0.415). e, Schematic of α-KG binding interactions. f, Cell-based transport assays for wild-type (WT) and mutant human OAT1. n = 15 independent experiments for the mutants and 80 for the wild type, errors shown are s.d. Inset shows IC50 for α-KG for wild-type and Gly227Ala mutant n = 4, data are mean ± s.d.
