Fig. 2.

The binding mode of DH. In (A) the 2D structure of DH with five key binding groups (a–e) are highlighted and in (B) the binding interactions of DH with GluK1–LBC are shown in detail. (a) The side chain guanidinium group of Arg523 and Ser689^N, and Thr518^N hydrogen bond to the α-carboxylate group of DH and the side chain carboxylate group of Glu738, the side chain hydroxyl of Thr518, and Pro516^O hydrogen bond to the α-amine group of DH. (b) Thr690^N and the side chain hydroxyl of Thr690 hydrogen bond to the γ-carboxylate group of DH. (c) The C8 aminomethyl group hydrogen bonds to the side chain hydroxyl of Ser741 and the side chain carboxylate group of Glu738, and (d) the C9 hydroxyl of the ring system hydrogen bond to Glu738^N. (e) The tetrahydrofuropyran ring (referred as the ring system) of DH hydrophobically packs against the side chains of the binding pocket residues Tyr489, Glu441, and Pro516 at the D1 face of the binding pocket. The hydrogen bonds are shown as green dotted lines, the yellow line represent intra-ligand hydrogen bonds, the orange lines highlight the hydrogen bonds between the side chains of Glu441 and Ser721, and the purple line connect Glu738^N to the C9 hydroxyl. The solvent accessible surface (transparent surface) visualizes the hydrophobic face. Amino acids at the D1 face are shown with white carbon atoms and at the D2 face with black carbon atoms. The oxygen atom of the water molecule is presented as red sphere, and the ligand skeleton is shown as yellow ball-and-stick representation.