Molecular recognition of fatty acids by peroxisome proliferator- activated receptors

H. Eric Xu, Millard H. Lambert, Valerie G. Montana, Derek J. Parks, Steven G. Blanchard, Peter J. Brown, Daniel D. Sternbach, Jürgen M. Lehmann, G. Bruce Wisely, Timothy M. Willson, Steven A. Kliewer, Michael V. Milburn

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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 PPARδ ligand-binding domain (LBD) bound to either the FA eicosapentaenoic acid (EPA) or the synthetic fib rate 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.

Original languageEnglish (US)
Pages (from-to)397-403
Number of pages7
JournalMolecular Cell
Volume3
Issue number3
DOIs
StatePublished - Mar 1999

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Peroxisome Proliferator-Activated Receptors
Eicosapentaenoic Acid
Fatty Acids
Cytoplasmic and Nuclear Receptors
Carboxylic Acids
Molecular Structure
Homeostasis
Ligands
Lipids
Glucose

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Xu, H. E., Lambert, M. H., Montana, V. G., Parks, D. J., Blanchard, S. G., Brown, P. J., ... Milburn, M. V. (1999). Molecular recognition of fatty acids by peroxisome proliferator- activated receptors. Molecular Cell, 3(3), 397-403. https://doi.org/10.1016/S1097-2765(00)80467-0

Molecular recognition of fatty acids by peroxisome proliferator- activated receptors. / Xu, H. Eric; Lambert, Millard H.; Montana, Valerie G.; Parks, Derek J.; Blanchard, Steven G.; Brown, Peter J.; Sternbach, Daniel D.; Lehmann, Jürgen M.; Wisely, G. Bruce; Willson, Timothy M.; Kliewer, Steven A.; Milburn, Michael V.

In: Molecular Cell, Vol. 3, No. 3, 03.1999, p. 397-403.

Research output: Contribution to journalArticle

Xu, HE, Lambert, MH, Montana, VG, Parks, DJ, Blanchard, SG, Brown, PJ, Sternbach, DD, Lehmann, JM, Wisely, GB, Willson, TM, Kliewer, SA & Milburn, MV 1999, 'Molecular recognition of fatty acids by peroxisome proliferator- activated receptors', Molecular Cell, vol. 3, no. 3, pp. 397-403. https://doi.org/10.1016/S1097-2765(00)80467-0
Xu HE, Lambert MH, Montana VG, Parks DJ, Blanchard SG, Brown PJ et al. Molecular recognition of fatty acids by peroxisome proliferator- activated receptors. Molecular Cell. 1999 Mar;3(3):397-403. https://doi.org/10.1016/S1097-2765(00)80467-0
Xu, H. Eric ; Lambert, Millard H. ; Montana, Valerie G. ; Parks, Derek J. ; Blanchard, Steven G. ; Brown, Peter J. ; Sternbach, Daniel D. ; Lehmann, Jürgen M. ; Wisely, G. Bruce ; Willson, Timothy M. ; Kliewer, Steven A. ; Milburn, Michael V. / Molecular recognition of fatty acids by peroxisome proliferator- activated receptors. In: Molecular Cell. 1999 ; Vol. 3, No. 3. pp. 397-403.
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