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 Citations (Scopus)

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

Fingerprint

Cholecystokinin Receptors
Molecular Models
Benzodiazepines
Ligands
Molecules
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Molecular basis for benzodiazepine agonist action at the type 1 cholecystokinin receptor. / Harikumar, Kaleeckal G.; Cawston, Erin E.; Lam, Polo C H; Patil, Achyut; Orry, Andrew; Henke, Brad R.; Abagyan, Ruben; Christopoulos, Arthur; Sexton, Patrick M.; Miller, Laurence J.

In: Journal of Biological Chemistry, Vol. 288, No. 29, 19.07.2013, p. 21082-21095.

Research output: Contribution to journalArticle

Harikumar, KG, Cawston, EE, Lam, PCH, Patil, A, Orry, A, Henke, BR, Abagyan, R, Christopoulos, A, Sexton, PM & Miller, LJ 2013, 'Molecular basis for benzodiazepine agonist action at the type 1 cholecystokinin receptor', Journal of Biological Chemistry, vol. 288, no. 29, pp. 21082-21095. https://doi.org/10.1074/jbc.M113.480715
Harikumar, Kaleeckal G. ; Cawston, Erin E. ; Lam, Polo C H ; Patil, Achyut ; Orry, Andrew ; Henke, Brad R. ; Abagyan, Ruben ; Christopoulos, Arthur ; Sexton, Patrick M. ; Miller, Laurence J. / Molecular basis for benzodiazepine agonist action at the type 1 cholecystokinin receptor. In: Journal of Biological Chemistry. 2013 ; Vol. 288, No. 29. pp. 21082-21095.
@article{471c6c2c79d741c4ba45824cb2ecb7e9,
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.",
author = "Harikumar, {Kaleeckal G.} and Cawston, {Erin E.} and Lam, {Polo C H} and Achyut Patil and Andrew Orry and Henke, {Brad R.} and Ruben Abagyan and Arthur Christopoulos and Sexton, {Patrick M.} and Miller, {Laurence J}",
year = "2013",
month = "7",
day = "19",
doi = "10.1074/jbc.M113.480715",
language = "English (US)",
volume = "288",
pages = "21082--21095",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "29",

}

TY - JOUR

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.

UR - http://www.scopus.com/inward/record.url?scp=84880526901&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880526901&partnerID=8YFLogxK

U2 - 10.1074/jbc.M113.480715

DO - 10.1074/jbc.M113.480715

M3 - Article

C2 - 23754289

AN - SCOPUS:84880526901

VL - 288

SP - 21082

EP - 21095

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 29

ER -