Substitution of a conserved amino acid residue alters the ligand binding properties of peroxisome proliferator activated receptors

FEBS Letters

Palmer, Colin N.A.¹  Causevic, Mirsada¹  Wolf, C.Roland¹ 

[1] Biomedical Research Centre and ICRF Molecular Pharmacology Unit, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK

关键词: Nuclear receptor;    Peroxisome proliferator;    Fatty acid;    Fluorescence;    Thiazolidinedione;    Diabetes;    CPA;    cis-parinaric acid;    EPA;    eicosapentanoic acid;    PPAR;    peroxisome proliferator activated receptor;    ER;    oestrogen receptor;    TR;    thyroid hormone receptor;    RAR;    retinoic acid receptor;    RXR;    retinoid X receptor;    LBD;    ligand binding domain;   

DOI  :  10.1016/S0014-5793(99)01618-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Mutation of glutamic acid 282 of PPARα to glycine has been shown to result in an increased EC₅₀ 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.

【 授权许可】

Unknown