Balanol and the hGRK2·balanol complex. a) Chemical structure of balanol, with A, B, C, and D rings labeled. b) Balanol bound in the active site of hGRK2. Electron density from a 2.9 Å |F_o|-|F_c| omit map (blue cage) is drawn at the 3σ level. Balanol is drawn with carbons colored tan, oxygens red, and nitrogens cyan. c) Comparison of apo hGRK2 (black Cα trace) with hGRK2·balanol (yellow Cα trace). The small lobes of the structures were superimposed. Conformational changes are observed in the P-loop, the αB–αC loop of the small lobe, and the kinase domain adopts a slightly more closed conformation when in complex with balanol. d) Comparison of the hGRK2·balanol and PKA·balanol complexes. The PKA·balanol complex (PDB entry 1BX6) is shown with grey carbons. hGRK2-Val255 is displaced into the binding pocket relative to its equivalent in PKA (Val104), forcing an upwards tilt of the A ring. The benzophenone moiety is displaced towards the large lobe (bottom of figure) relative to PKA. Residues that contact the benzophenone moiety in hGRK2 are substituted by shorter side chains relative to PKA: hGRK2-Gly201 (PKA-Ser53) in the P-loop, hGRK2-Gly232 (PKA-Gln84) in αB, hGRK2-Leu235 (PKA-His87) and hGRK2-Ala236 (PKA-Thr88) in αC, and hGRK2-Leu338 (PKA-Phe187) in the large lobe. Hydrogen bonds between hGRK2 and balanol are shown with black dashed lines. One hydrogen bond, shown in green, is unique to the PKA complex.