Figure 3. Binding of various oxidized fatty acid ligands to PPARγ.
(a) Electron density maps with refined models of 5-HEPA, 4-HDHA, 4-oxoDHA and 6-oxoOTE bound to the PPARγ LBD. Note the 4-oxoDHA and 6-oxoOTE ligands are covalently coupled to Cys285. For orientation the end-on view of helix 3 is indicated by a magenta ellipsoid. The refmac weighted maps are contoured at 0.8 sigma. (b) Maldi-ToF mass spectrometry of ligands bound to PPARγ shows that the oxidized fatty acids are covalently coupled to the LBD. (c) Mechanism of Michael addition for covalent binding of oxidized fatty acid ligands to PPARγ.