2GWX

MOLECULAR RECOGNITION OF FATTY ACIDS BY PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS

Summary for 2GWX

• Entry DOI: 10.2210/pdb2gwx/pdb
• Descriptor: PROTEIN (PPAR-DELTA) (2 entities in total)
• Functional Keywords: ppar, fatty acids, transcription, nuclear receptor fold
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q03181
• Total number of polymer chains: 2
• Total formula weight: 61137.18

Authors

Xu, H.E.,Lambert, M.H.,Montana, V.G.,Park, D.J.,Blanchard, S.,Brown, P.,Sternbach, D.,Lehmann, J.,Bruce, G.W.,Willson, T.M.,Kliewer, S.A.,Milburn, M.V. (deposition date: 1999-03-11, release date: 2000-03-11, Last modification date: 2023-12-27)

Primary citation

Xu, H.E.,Lambert, M.H.,Montana, V.G.,Parks, D.J.,Blanchard, S.G.,Brown, P.J.,Sternbach, D.D.,Lehmann, J.M.,Wisely, G.B.,Willson, T.M.,Kliewer, S.A.,Milburn, M.V.
Molecular recognition of fatty acids by peroxisome proliferator-activated receptors.
Mol.Cell, 3:397-403, 1999

PubMed 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.

PubMed: 10198642
DOI: 10.1016/S1097-2765(00)80467-0

Experimental method

X-RAY DIFFRACTION (2.3 Å)