Hudson, B. D. , Shimpukade, B., Milligan, G. and Ulven, T. (2014) The molecular basis of ligand interaction at free fatty acid receptor 4 (FFA4/GPR120). Journal of Biological Chemistry, 289, pp. 20345-20358. (doi: 10.1074/jbc.M114.561449) (PMID:24860101) (PMCID:PMC4106347)
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Abstract
The long-chain fatty acid receptor FFA4(previously GPR120) is receiving substantial interest as a novel target for the treatment of metabolic and inflammatory disease. The current study examines for the first time the detailed mode of binding of both a long-chain fatty acid and synthetic agonist ligands at FFA4 by integrating molecular modeling, receptor mutagenesis, and ligand structure-activity relationship approaches in an iterative format. In doing so, residues required for binding of fatty acid and synthetic agonists to FFA4 have been identified. This has allowed for the refinement of a well-validated model of the mode of ligand-FFA4 interaction which will be invaluable in the identification of novel ligands and future development of this receptor as a therapeutic target. The model reliably predicted the effects of substituent variations on agonist potency, and was also able to predict the qualitative effect of binding site mutations in the majority of cases.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Hudson, Dr Brian and Milligan, Professor Graeme |
Authors: | Hudson, B. D., Shimpukade, B., Milligan, G., and Ulven, T. |
College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
Journal Name: | Journal of Biological Chemistry |
Publisher: | American Society for Biochemistry and Molecular Biology, Inc. |
ISSN: | 0021-9258 |
ISSN (Online): | 1083-351X |
Copyright Holders: | Copyright © 2014 The Authors |
First Published: | First published in Journal of Biological Chemistry 289:20345-20358 |
Publisher Policy: | Reproduced under a Creative Commons License |
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