The effect of charge reversal mutations in the ?-helical region of liver fatty acid binding protein on the binding of fatty-acyl CoAs, lysophospholipids and bile acids
The effect of charge reversal mutations in the ?-helical region of liver fatty acid binding protein on the binding of fatty-acyl CoAs, lysophospholipids and bile acids
Liver fatty acid binding protein (LFABP) is unique among the various types of FABPs in that it can bind a variety of ligands in addition to fatty acids. LFABP is able to bind long chain fatty acids with a 2:1 stoichiometry and the crystal structure has identified two fatty acid binding sites in the binding cavity. The presumed primary site (site 1) involves the fatty acid binding with the carboxylate group buried in the cavity whereas the fatty acid at site 2 has the carboxylate group solvent-exposed within the ligand portal region and in the vicinity of ?-helix II. The ?-helical region contains three cationic residues, K20, K31, K33 and modelling studies suggest that K31 on ?-helix II could make an electrostatic contribution to anionic ligands binding to site 2. The preparation of three charge reversal mutants of LFABP, K20E, K31E and K33E has allowed an investigation of the role of site 2 in ligand binding, particularly those ligands with a bulky anionic head group. The binding of oleoyl CoA, lysophosphatidic acid, lysophosphatidylcholine, lithocholic acid and taurolithocholate 3-sulphate to LFABP has been studied using the ?-helical mutants. The results support the concept that such ligands bind at site 2 of LFABP where solvent exposure allows the accommodation of their bulky anionic group.
liver fabp, lysophospholipid, bile acid, acyl coa, dauda, charge reversal mutagenesis
55-60
Hagan, Robert
44a38ff3-b7fd-4ddf-a16e-d875c00416ee
Davies, Joanna K.
dfb115c1-758a-4479-a5bb-ed0d2d969c77
Wilton, David C.
4b995f66-ad6c-4d96-9179-c64f3b54466a
2002
Hagan, Robert
44a38ff3-b7fd-4ddf-a16e-d875c00416ee
Davies, Joanna K.
dfb115c1-758a-4479-a5bb-ed0d2d969c77
Wilton, David C.
4b995f66-ad6c-4d96-9179-c64f3b54466a
Hagan, Robert, Davies, Joanna K. and Wilton, David C.
(2002)
The effect of charge reversal mutations in the ?-helical region of liver fatty acid binding protein on the binding of fatty-acyl CoAs, lysophospholipids and bile acids.
Molecular and Cellular Biochemistry, 239 (1/2), .
(doi:10.1023/A:1020562808304).
Abstract
Liver fatty acid binding protein (LFABP) is unique among the various types of FABPs in that it can bind a variety of ligands in addition to fatty acids. LFABP is able to bind long chain fatty acids with a 2:1 stoichiometry and the crystal structure has identified two fatty acid binding sites in the binding cavity. The presumed primary site (site 1) involves the fatty acid binding with the carboxylate group buried in the cavity whereas the fatty acid at site 2 has the carboxylate group solvent-exposed within the ligand portal region and in the vicinity of ?-helix II. The ?-helical region contains three cationic residues, K20, K31, K33 and modelling studies suggest that K31 on ?-helix II could make an electrostatic contribution to anionic ligands binding to site 2. The preparation of three charge reversal mutants of LFABP, K20E, K31E and K33E has allowed an investigation of the role of site 2 in ligand binding, particularly those ligands with a bulky anionic head group. The binding of oleoyl CoA, lysophosphatidic acid, lysophosphatidylcholine, lithocholic acid and taurolithocholate 3-sulphate to LFABP has been studied using the ?-helical mutants. The results support the concept that such ligands bind at site 2 of LFABP where solvent exposure allows the accommodation of their bulky anionic group.
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Published date: 2002
Keywords:
liver fabp, lysophospholipid, bile acid, acyl coa, dauda, charge reversal mutagenesis
Organisations:
Centre for Biological Sciences
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Local EPrints ID: 372328
URI: http://eprints.soton.ac.uk/id/eprint/372328
ISSN: 0300-8177
PURE UUID: 67dbb867-13aa-4a2c-9ef9-48b3b33c0564
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Date deposited: 01 Dec 2014 11:53
Last modified: 14 Mar 2024 18:34
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Author:
Robert Hagan
Author:
Joanna K. Davies
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