Molecular recognition of fatty acids by peroxisome proliferator-activated receptors.

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Xu HE, Lambert MH, Montana VG, Parks DJ, Blanchard SG, Brown PJ, Sternbach DD, Lehmann JM, Wisely GB, Willson TM, Kliewer SA, Milburn MV

Molecular recognition of fatty acids by peroxisome proliferator-activated receptors.

Mol Cell. 1999 Mar;3(3):397-403.

PubMed ID

10198642 [ View in PubMed

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Abstract

The peroxisome proliferator-activated receptors (PPARs) are nuclear receptors for fatty acids (FAs) that regulate glucose and lipid homeostasis. We report the crystal structure of the PPAR delta ligand-binding domain (LBD) bound to either the FA eicosapentaenoic acid (EPA) or the synthetic fibrate GW2433. The carboxylic acids of EPA and GW2433 interact directly with the activation function 2 (AF-2) helix. The hydrophobic tail of EPA adopts two distinct conformations within the large hydrophobic cavity. GW2433 occupies essentially the same space as EPA bound in both conformations. These structures provide molecular insight into the propensity for PPARs to interact with a variety of synthetic and natural compounds, including FAs that vary in both chain length and degree of saturation.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Icosapent	Peroxisome proliferator-activated receptor delta	Protein	Humans	Yes	Agonist	Details

Polypeptides

Name	UniProt ID
Peroxisome proliferator-activated receptor delta	Q03181	Details