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

Mirsada Causevic, C. Roland Wolf, Colin N.A. Palmer (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    8 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)205-210
    Number of pages6
    JournalFEBS Letters
    Volume463
    Issue number3
    DOIs
    Publication statusPublished - 17 Dec 1999

    Keywords

    • Diabetes
    • Fatty acid
    • Fluorescence
    • Nuclear receptor
    • Peroxisome proliferator
    • Thiazolidinedione

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