Detail of "136381-85-6"

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Identification of two amino acids of the human cholecystokinin-A receptor that interact with the N-terminal moiety of cholecystokinin

Identification of two amino acids of the human cholecystokinin-A receptor that interact with the N-terminal moiety of cholecystokinin. Kennedy, Karen; Gigoux, Veronique; Escrieut, Chantal; Maigret, Bernard; Martinez, Jean; Moroder, Luis; Frehel, Daniel; Gully, Danielle; Vaysse, Nicole; Fourmy, Daniel (INSERM U151, Inst. Louis Bugnard, Toulouse 31054, Fr.). Journal of Biological Chemistry, 272(5), 2920-2926 (English) 1997 American Society for Biochemistry and Molecular Biology. CODEN: JBCHA3. ISSN: 0021-9258. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) A region between residues 38 and 42 of the human cholecystokinin-A (CCK-A) receptor was shown to be involved in the binding of CCK but not in that of JMV 179 and JMV 180, two peptides closely related to CCK (K. Kennedy, et al., 1995). In the present study, we have identified the residues of both the receptor and the ligand responsible for this differential binding.In this article, certain chemicals are used. Some of their cas registry numbers are 136381-85-6 and 77568-41-3 Residues Trp-39 and Gln-40 of the receptor were crucial for binding of the C-terminal nonapeptide of CCK as W39F and Q40N mutants demonstrated parallel decreases in both affinity and potency to induce accumulation of inositol phosphates (12.9- and 20.9-fold). The W39F and Q40N mutant receptors bound CCK analogs modified at their C-terminal end, including JMV 179 and JMV 180, as well as the C-terminal amidated heptapeptide of CCK, with identical affinities to the wild-type receptor. In contrast, W39F and Q40N mutants bound CCK octapeptide with the same decreased affinity as the CCK nonapeptide. The modeling of the CCK-A receptor and the docking of the peptide agonists [Thr4,Nle7]CCK9 and CCK-8 indicated that their N terminus was connected to the receptor through a strong bond network involving Trp-39 and Gln-40 thus confirming exptl. data. These first mol. data identifying the agonist binding site of the human CCK-A receptor represent an important step toward the complete delineation of the agonist binding site and the understanding of the mol. mechanisms that govern differential activation of this receptor by CCK-related peptides. .