Figure 3

Binding orientations of compounds JAGC_7 and DPU-2 in the binding pocket of GuaB2.
(A and B) Orientation of JAGC_7 (cyan) in the IMP site. Its 4-methyl cyclohexane ring occupies the xanthosine subsite and forms π-π stacking with the nicotinamide moiety of NAD+ and GuaB2-JAGC_7 interactions. Green sticks represent the NAD+ molecule. (C and D) Orientation of JAGC_7 in the NAD+ binding site where the 1,2,3,benzothiadiazole ring occupies the nicotinamide position and forms π-π bonds with IMP (brown sticks), and its interactions with binding site residues. (E and F) Binding orientation of DPU-2 (magenta) and its interactions of in the IMP binding site. The nitrophenyl moiety is positioned towards the nicotinamide scaffold of NAD+. (G and H) Binding orientation and interactions of DPU-2 in the NAD+ binding site. The nitrophenyl group is π stacking with the purin-6-one ring. In the interaction figures B, D, F and H, the red dotted lines represent hydrophobic interactions including π-π interactions between the inhibitor and the residues in the GuaB2 binding pockets and hydrogen bonds are shown by the dashed blue line.