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Substitution of a conserved amino acid residue alters the ligand binding properties of peroxisome proliferator activated receptors
Author(s) -
Causevic Mirsada,
Wolf C.Roland,
Palmer Colin N.A.
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01618-x
Subject(s) - ligand (biochemistry) , mutant , receptor , glutamic acid , chemistry , peroxisome proliferator activated receptor , biochemistry , amino acid , peroxisome , binding site , stereochemistry , gene
Mutation of glutamic acid 282 of PPARα 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 mPPARα and hPPARγ for the fluorescent fatty acid, cis ‐parinaric acid and that the mutant hPPARγ 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.