Molecular basis for benzodiazepine agonist action at the type 1 cholecystokinin receptor

Kaleeckal G. Harikumar, Erin E. Cawston, Polo C.H. Lam, Achyut Patil, Andrew Orry, Brad R. Henke, Ruben Abagyan, Arthur Christopoulos, Patrick M. Sexton, Laurence J. Miller

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Background: Cholecystokinin receptor type 1 (CCK1R) stimulates satiety. Results: Binding and activity of a CCK1R agonist/CCK2R antagonist are studied at wild-type and chimeric receptors, and ligand-guided model refinement is utilized. Conclusion: The small molecule agonist docking site is distinct from the antagonist site, with benzodiazepines docked with consistent pose, including approximation with Leu7.39. Significance: The molecular model and determinants for small molecule agonist action should facilitate drug development.

Original languageEnglish (US)
Pages (from-to)21082-21095
Number of pages14
JournalJournal of Biological Chemistry
Volume288
Issue number29
DOIs
StatePublished - Jul 19 2013

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Harikumar, K. G., Cawston, E. E., Lam, P. C. H., Patil, A., Orry, A., Henke, B. R., Abagyan, R., Christopoulos, A., Sexton, P. M., & Miller, L. J. (2013). Molecular basis for benzodiazepine agonist action at the type 1 cholecystokinin receptor. Journal of Biological Chemistry, 288(29), 21082-21095. https://doi.org/10.1074/jbc.M113.480715