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, bond between the -NH amide and a carbonyl or methoxy group, respectively. BIMU8 elicits 5-HT4R activation by forming a hydrogen bond interaction with W6, p.while

, S-zacopride triggers activation via the interaction with T3.36 in the active g+ conformation (B). The atoms implicated in these interactions are pointed out: oxygen of the drugs is asterisked and T3, vol.36

, cAMP accumulation at different densities of 5-HT4-W6.48A mutant

, *Data are expressed as a percentage of maximal stimulation due to 5-HT in W6.48A mutant expressing the highest receptor density (6490 fmol/mg protein), cells, was measured over 10 min-stimulation induced by 5-HT (A) or BIMU8 (B), vol.500, 1000.

, In the absence of W6.48, the aromatic ring of BIMU8 occupies the position of the active t conformation of W6.48 in the WT receptor (see Fig. 5C); and the carbonylic oxygen hydrogen bonds the active g+ rotamer of T3.36. The atoms implicated in this interaction are pointed out: oxygen of the drug is asterisked and T3, Computational models of the complex between BIMU8 and W6.48A mutant receptor