Figure 1.
Chemical structures of adrenergic ligands.
Chemical structures of the co-crystallized inverse agonists S-carazolol (left) and S-cyanopindolol (center) and of the full agonist R-isoprenaline (right). In the green oval, the C-C-O-H motif discussed in the Results section is highlighted.
Figure 2.
Transmembrane region and binding pocket root mean square deviation.
Root mean square deviation (RMSD) of backbone atoms of all alpha helices (left) and of residues in the binding site (right) for unliganded β2AR (black), unliganded β1AR (blue), isoprenaline-bound β2AR (green) and isoprenaline-bound β1AR (red).
Figure 3.
Agonist interactions with helices V and VI.
MD snapshots of the hydrogen-bond interaction network between isoprenaline and Ser(5.42), Ser(5.43), Ser(5.47), Asn(6.55), Tyr/Phe(7.35) and internal water molecules in β2AR (left) and β1AR (right).
Figure 4.
Agonist interactions with helices III and VII.
Panel A: Hydrogen-bond interaction network between Asp(3.32) and Asn(7.39) and carazolol in β2AR (left) and cyanopindolol in β1AR (right). Panel B: MD snapshot of the hydrogen-bond interaction network between isoprenaline and Asp(3.32), Asn(7.39) and internal water molecules in β2AR (left) and β1AR (right).
Table 1.
Ligand C-C-O-H dihedral angle populations.
Figure 5.
Conformations of second extracellular loop in β2AR.
Conformation of the second extracellular loop (ECL2) and of Phe193 (sticks representation) in MD simulations of unliganded β2AR (yellow), carazolol-bound β2AR (blue) and isoprenaline-bound β2AR (red). Isoprenaline and carazolol are shown in transparency. Root mean square fluctuations are shown in Figure S5 of Supplementary Information.
Figure 6.
Conformations of third extracellular loop in β1AR.
Conformation of the third extracellular loop (ECL3) and of Phe315 and Asn(6.55) (sticks representation) in MD simulations of unliganded β1AR (yellow), cyanopindolol-bound β1AR (blue) and isoprenaline-bound β1AR (red). Isoprenaline and cyanopindolol are shown in transparency.