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NRS 13, e004 | Figure 3

Puhl A, Milton F, Cvoro A, Sieglaff D, Campos J, Bernardes A, Filguiera C, Lindemann JL, Deng T, Neves F, Polikarpov I and Webb P (2015) Mechanisms of peroxisome proliferator activated receptor γ regulation by non-steroidal antiinflammatory drugs. Nucl Recept Sig 13, e004. doi:10.1621/nrs.13004


Figure 3. Chemical structures and formulae of NSAIDs diclofenac, indomethacin and sulindac sulfide. Oxygen atoms are shaded in red, including those of the carboxylate acidic group that is a common feature of ligands that bind PPARs. (B) Superposition of NSAIDs bound to PPARγ. In Chain A, the indomethacin and sulindac sulfide are bound to site 1, near H12, in a conserved binding mode, making hydrogen bonds with Y473 (H12), H449, H323 and S289, that are canonical interactions found for full agonists. In Chain B, helix 12 is an inactive conformation and sulindac sulfide bound to site 1 adopted a different bound conformation in comparison to Chain A, with interactions with Y473 and S289 not available. NSAIDs adopt different binding modes to site 2 in Chains A and B. Indomethacin and sulindac sulfide display similar binding modes at site 2 in chain A. Although indomethacin adopts the same conformation for site 2 in both chains, sulindac sulfide adopts different positions. Diclofenac is only detected at Chain B site 2 and adopts a distinct position from the other NSAIDs.