title: Substitution of a conserved amino acid residue alters the ligand binding properties of peroxisome proliferator activated receptors.
abstract: Mutation of glutamic acid 282 of PPARalpha to glycine has been shown to result in an increased EC(50) for a wide variety of PPAR activating compounds. This has suggested that mutant receptor has a reduced ability to bind ligand. In this study we show that this mutation reduces the affinity of mPPARalpha and hPPARgamma for the fluorescent fatty acid, cis-parinaric acid and that the mutant hPPARgamma protein has a reduced affinity for the radiolabelled compound, SB236636. These data confirm the role of this glutamic acid in ligand binding and support recent crystal structure observations regarding a proposed novel mode of ligand entry into the PPAR ligand binding cavities.
authors.affiliation: Biomedical Research Centre, ICRF Molecular Pharmacology Unit, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
authors.forename: M
authors.initials: M
authors.lastname: Causevic
authors.forename: C R
authors.initials: CR
authors.lastname: Wolf
authors.forename: C N
authors.initials: CN
authors.lastname: Palmer
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D004926:Escherichia coli; D005231:Fatty Acids, Unsaturated / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D015870:Gene Expression; D018698:Glutamic Acid / Q000737:chemistry; D006801:Humans; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000235:genetics; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics
chemical_list: D000596:Amino Acids; D005231:Fatty Acids, Unsaturated; D005456:Fluorescent Dyes; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D018698:Glutamic Acid; C013641:parinaric acid