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

doi:10.1074/jbc.M113.480715

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 journal › Article › peer-review

13 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 language	English (US)
Pages (from-to)	21082-21095
Number of pages	14
Journal	Journal of Biological Chemistry
Volume	288
Issue number	29
DOIs	https://doi.org/10.1074/jbc.M113.480715
State	Published - Jul 19 2013

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Cell Biology

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title = "Molecular basis for benzodiazepine agonist action at the type 1 cholecystokinin receptor",

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.",

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T1 - Molecular basis for benzodiazepine agonist action at the type 1 cholecystokinin receptor

AU - Harikumar, Kaleeckal G.

AU - Cawston, Erin E.

AU - Lam, Polo C.H.

AU - Patil, Achyut

AU - Orry, Andrew

AU - Henke, Brad R.

AU - Abagyan, Ruben

AU - Christopoulos, Arthur

AU - Sexton, Patrick M.

AU - Miller, Laurence J.

PY - 2013/7/19

Y1 - 2013/7/19

N2 - 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.

AB - 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.

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

Abstract

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