Fig. 3: Antagonism of URAT1EM by lesinurad and its analog verinurad.
a Chemical structure and cryo-EM density of lesinurad and verinurad. b Coronal section view of electrostatic surface of URAT1LES and URAT1VER. Benzbromarone is represented as spheres. c cytoplasmic view of URAT1 in complex with lesinurad and verinurad. d Detailed view of the lesinurad binding pocket. Surrounding residues are represented as sticks. Hydrogen bond is depicted as black dash line. Inhibition of 14C-urate transport by lesinurad e and verinurad h in URAT1EM and its mutants. Data are presented as normalized mean ± s.e.m. from three biologically independent assays (n = 3). IC50 values are calculated by fitting into a nonlinear regression model. f Detailed view of the verinurad binding pocket. Surrounding residues are represented as sticks. Hydrogen bond is depicted as black dash line. g Superposition between URAT1LES and URAT1VER binding pocket. The key residues are shown as sticks. Lesinurad and verinurad are colored purple and yellow, respectively.
