FIGURE 3. Clomipramine-binding site.

From the following article:

Antidepressant binding site in a bacterial homologue of neurotransmitter transporters

Satinder K. Singh, Atsuko Yamashita & Eric Gouaux

Nature 448, 952-956(23 August 2007)



a, Stereo view, with clomipramine and leucine carbon atoms depicted in yellow, sodium ions in purple and two water molecules in red. Residues whose interactions with clomipramine are hydrophobic, polar (Q34) or ionic (D401) are coloured grey, orange and pink, respectively. Atoms depicted as spheres interact through either a hydrogen bond or a salt bridge. b, FoFc simulated annealing omit map, contoured at 3.0 sigma, of D404 and R30, depicting the direct salt bridge between the guanidium of R30 and the carboxylate of D404, with displacement of two water molecules (compare to overlay in d). Distances (Å) are shown along dashed lines. c, FoFc simulated annealing omit map, contoured at 3.0 sigma, of the tip of EL4 (residues A317–N321), illustrating the movement 'up' of A319 in the LeuT–clomipramine crystal structure (compare to overlay in d). d, Same view as in a with residues from the original LeuT structure (PDB ID 2A65) overlaid (in green with two water molecules between D404 and R30 in cyan) onto those from the LeuT–clomipramine crystal structure (in pink with the two displaced waters in red and labelled as H2O (CMI)). e, CPK rendering of clomipramine, R30 and F253 illustrating how the positively charged guanidium group is sandwiched between the aromatic rings of clomipramine and F253.