Fig. 2.
Crystal structure of OX1R in complex with the selective antagonist JH112. (A) Overall structure of the OX1R-PGS-JH112 complex. (B and C) Binding pocket of OX1R interacting with JH112. (D and E) Interaction of JH112 with the nonconserved position in TM3 of OX1R and OX2R. (D) The crystal structure shows the (S,S)-sec-butyl substituent of JH112 pointing directly to the nonconserved Ala3.33 in OX1R without leading to a steric clash between the ligand and the receptor. (E) Superimposition of the OX2R structure on the OX1R-JH112 structure indicates repulsive interactions between Thr3.33 of the OX2R and the (S,S)-sec-butyl substituent of JH112.