Fig. 2: (+)-Cyclazosin binding pocket in α_1BAR_XTAL.

a Detailed view of the (+)-cyclazosin binding site. (+)-Cyclazosin is shown as sticks in cyan, with the two alternative orientations observed for the furan-2-yl-methanone substituent (highlighted by a dashed red ellipse) colored in cyan (on the left) and pale cyan (on the right), respectively. Receptor residues are shown as sticks in pale green except for the F334→L mutation, which is colored in dark gray and is indicated by an asterisk. V197 is shown to Cβ only because its side chain is not resolved in the electron density map. Hydrogen bonds are depicted as dashed blue lines. Oxygen, nitrogen, and sulfur atoms are depicted in red, blue, and yellow, respectively. b MD simulation of α_1BAR_XTAL-MD-V333-F334. The plots on the right indicate the structural stability of (+)-cyclazosin and F334_MD throughout the simulation. RMSD, root-mean-square deviation; g⁻, gauche minus conformation of the χ₁ dihedral angle. For (+)-cyclazosin, RMSD values were calculated on all atoms. A representative snapshot of the final nanosecond of the simulation is depicted on the left, viewed from the same perspective as in panel a. (+)-Cyclazosin is colored in teal; F334_MD is colored in dark green. c Schematic representation of the (+)-cyclazosin binding site. OBS, orthosteric binding site; SBPs, secondary binding pockets. A black curved arrow indicates the two orientations observed for the furan-2-yl-methanone moiety. Note that residues C195^45.50, G196^45.51, and V197^45.52 belong to ECL2, which forms crystal contacts. Source data are provided as a Source Data file.