Structural basis for the activation of peroxisome proliferator-activated receptor-gamma by telmisartan

Telmisartan, a selective angiotensin receptor blocker, has been recently shown to act as a partial agonist for peroxisome proliferator-activated receptor-gamma (PPARγ). To understand the activation mechanism of PPARγ by telmisartan, we determined the ternary complex structure of PPARγ, telmisartan and coactivator peptide from SRC1 at 2.25 A resolution. The overall fold of PPARγ is almost identical to previously-determined complex structures with agonists. However, telmisartan exhibits an unexpected binding mode, devoid of some essential hydrogen bonds for full activation of PPARγ.