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Probing the fibrate binding specificity of rat liver fatty acid binding protein

Citation

Chuang, S and Velkov, T and Horne, HJ and Wielens, J and Chalmers, DK and Porter, CJ and Scanlon, MJ, Probing the fibrate binding specificity of rat liver fatty acid binding protein, Journal of Medicinal Chemistry, 52, (17) pp. 5344-55. ISSN 0022-2623 (2009) [Refereed Article]

DOI: doi:10.1021/jm801349e5344-55

Abstract

Liver-fatty acid binding protein (L-FABP) is found in high levels in enterocytes and is involved in cytosolic solubilization of fatty acids. In addition, L-FABP has been shown to bind endogenous and exogenous lipophilic compounds, suggesting that it may also play a role in modulating their absorption and disposition within enterocytes. Previously, we have described binding of L-FABP to a range of drugs, including a series of fibrates. In the present study, we have generated structural models of L-FABP-fibrate complexes and undertaken thermodynamic analysis of the binding of fibrates containing either a carboxylic acid or ester functionality. Analysis of the current data reveals that both the location and the energetics of binding are different for fibrates that contain a carboxylate compared to those that do not. As such, the data presented in this study suggest potential mechanisms that underpin molecular recognition and dictate specificity in the interaction between fibrates and L-FABP.

Item Details

Item Type:Refereed Article
Keywords:ESCHERICHIA-COLI; LIGAND-BINDING; CRYSTAL-STRUCTURE; MULTIGENE FAMILY; MUTATIONS; RECEPTORS; HEART; COMPENSATION; EXPRESSION; ADIPOCYTE
Research Division:Chemical Sciences
Research Group:Medicinal and Biomolecular Chemistry
Research Field:Characterisation of Biological Macromolecules
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Biological Sciences
Author:Horne, HJ (Dr James Horne)
ID Code:74000
Year Published:2009
Web of Science® Times Cited:14
Deposited By:Central Science Laboratory
Deposited On:2011-11-04
Last Modified:2011-11-04
Downloads:0

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