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Molecular recognition of nitrated fatty acids by PPARγ

Nature Structural & Molecular Biology volume 15, pages 865–867 (2008)Cite this article

Abstract

Peroxisome proliferator activated receptor-γ (PPARγ) regulates metabolic homeostasis and adipocyte differentiation, and it is activated by oxidized and nitrated fatty acids. Here we report the crystal structure of the PPARγ ligand binding domain bound to nitrated linoleic acid, a potent endogenous ligand of PPARγ. Structural and functional studies of receptor-ligand interactions reveal the molecular basis of PPARγ discrimination of various naturally occurring fatty acid derivatives.

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Figure 1: The structure of the PPARγ LBD and LNO2 complex.
Figure 2: The structural determinants of the PPARγ LBD and LNO2 complex.
Figure 3: Functional correlation of the LNO2–PPARγ interactions.

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Acknowledgements

We thank W.D. Tolbert and Z. Wawrzak for assistance in data collection at the DND-CAT of the Advanced Photon Source. Use of the Advanced Photon Source was supported by the US Office of Science of the US Department of Energy. This work was supported in part by the Jay and Betty Van Andel Foundation (H.E.X.), US National Institutes of Health Grants DK071662 and DK066202 (H.E.X.), HL089301 (H.E.X. and Y.L.), HL68878, HL089544 and HL75397 (Y.E.C.), HL58115 and HL64937 (B.A.F.), American Diabetes Association (P.R.S.B.) and awards from the American Heart Association (Y.L., F.J.S.).

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Center for Pharmacogenetics, 709 Salk Hall, University of Pittsburgh, Pittsburgh, 15261, Pennsylvania, USA

    Yong Li & Dariusz Martynowski

  2. Laboratory of Structural Sciences, Van Andel Research Institute, Grand Rapids, 49503, Michigan, USA

    Yong Li, Amanda Kovach, Kelly Suino-Powell & H Eric Xu

  3. Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, 1150 West Medical Center Drive, Ann Arbor, 48109, Michigan, USA

    Jifeng Zhang & Y Eugene Chen

  4. Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, 15261, Pennsylvania, USA

    Francisco J Schopfer, Paul R S Baker & Bruce A Freeman

  5. Cardiovascular Research Institute, Morehouse School of Medicine, 720 Westview Drive SW, Atlanta, 30310, Georgia, USA

    Minerva T Garcia-Barrio

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  1. Yong Li
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Correspondence to Yong Li or H Eric Xu.

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Supplementary Figures 1–3, Supplementary Table 1 and Supplementary Methods (PDF 348 kb)

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Li, Y., Zhang, J., Schopfer, F. et al. Molecular recognition of nitrated fatty acids by PPARγ. Nat Struct Mol Biol 15, 865–867 (2008). https://doi.org/10.1038/nsmb.1447

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