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PDBsum entry 2vsr
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References listed in PDB file
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Key reference
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Title
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Structural basis for the activation of ppargamma by oxidized fatty acids.
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Authors
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T.Itoh,
L.Fairall,
K.Amin,
Y.Inaba,
A.Szanto,
B.L.Balint,
L.Nagy,
K.Yamamoto,
J.W.Schwabe.
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Ref.
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Nat Struct Biol, 2008,
15,
924-931.
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PubMed id
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Abstract
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The nuclear receptor peroxisome proliferator-activated receptor-gamma
(PPARgamma) has important roles in adipogenesis and immune response as well as
roles in both lipid and carbohydrate metabolism. Although synthetic agonists for
PPARgamma are widely used as insulin sensitizers, the identity of the natural
ligand(s) for PPARgamma is still not clear. Suggested natural ligands include
15-deoxy-delta12,14-prostaglandin J2 and oxidized fatty acids such as 9-HODE and
13-HODE. Crystal structures of PPARgamma have revealed the mode of recognition
for synthetic compounds. Here we report structures of PPARgamma bound to
oxidized fatty acids that are likely to be natural ligands for this receptor.
These structures reveal that the receptor can (i) simultaneously bind two fatty
acids and (ii) couple covalently with conjugated oxo fatty acids. Thermal
stability and gene expression analyses suggest that such covalent ligands are
particularly effective activators of PPARgamma and thus may serve as potent and
biologically relevant ligands.
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