Figure 5
Two-dimensional representation of the CCK-9 binding site in the CCK2R and CCK1R. Residues in the CCK2R and CCK1R (in red) reported to be in interaction with CCK-9 (in black) were indicated. For the CCK1R: Trp39 and Gln40 were shown in interaction with the N-terminal moiety of CCK-9 (Kennedy et al., 1997), Met195 with the Tyr3 aromatic ring (Gigoux et al., 1998), Arg197 with the Tyr3 sulfate group (Gigoux et al., 1999b; Ding et al., 2002), Arg336 (R6.58) and Asn333 (N6.55) with the Asp8 and C-terminal amide, respectively (Gigoux et al., 1999a), and several residues forming two hydrophobic pockets were identified in interaction with Met7 [Val125 (V3.61), Met121 (M3.57) and Ile352 (I7.35)] and Phe9 [Phe330 (F6.52), Val125 (V3.61) and Ile329 (I6.51)] (Escrieut et al., 2002). For the CCK2R: His207 was shown in interaction with Asp8 of CCK-9 (Silvente-Poirot et al., 1999). R57 (R1.35) was identified as important for CCK binding (Silvente-Poirot and Wank, 1996) and was shown to be part of the CCK2R sequence covalently linked to an N-terminal photoreactive CCK probe (Anders et al., 1999), and the current study shows interaction of Tyr189 (Y4.60) and Asn358 (N6.55) with the C-terminal amide of CCK. NT, N terminal; EL, extracellular loop.