Gw1929

Rosiglitazone

Fig. 12.8 Average difference in deuteration levels of PPARg LBD between ligand bound form and apo form [64]. Dark blue indicates the segment exchanges about the same rate with or without the ligand. Other colors indicate the segment exchanges slower with the ligand. Gray is the region not covered by the current experimental set [34].

the dynamics/conformation of PPARg LBD and consequently perturbs hydrogen exchange in various regions of the protein (Fig. 12.8). The degree to which different kind of ligands perturb PPARg LBD is distinguishable through H/D exchange. Three types of ligands were tested: (1) full agonists, rosiglitazone and GW1929; (2) partial agonist, nTZDpa; and (3) covalent antagonist, GW9662. Full agonists slowed exchange in wider regions and did it more strongly than either the partial agonist or the antagonist. This indicates the full agonist rigidifies the PPARg LBD more extensively than the other two, and is consistent with the NMR cross-peak analysis [61]. One very interesting observation is that the two full agonists rigidified helix 12 significantly while the partial agonist and the antagonist did not perturb the H/D exchange of that region.

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