Figure 6.

Binding site of macrocyclic Gα_q protein inhibitors and inhibitor-protein interactions

(A) Binding site of YM (magenta) at the heterotrimeric Gα_qβ₁γ₂ protein (Gα_q cyan, Gβ₁ light gray, Gγ₂ dark gray) as determined by X-ray crystallography (PDB: 3AH8).³⁶ Guanosine diphosphate is shown in yellow. A close-up illustrating the binding pose of YM, highlighting the amino acids Arg60 and Glu191, at the membrane is displayed at the right.

(B) 2D-ligand interaction diagram of YM at the binding pocket of the Gα_q protein, generated by Molecular Operating Environment (Chemical Computing Group, Cambridge, UK). See also Figures S1–S4 for ligand-binding site interactions of YM and FR derivatives.