Structural highlights
This is an X-ray crystallography structure, solved at 1.95 Å, which models the region of PPARδ from Gln171 to Tyr441[1]. It is composed of , with one small . The structure is bound to a synthetic ligand, , which contains a carboxylate group, a thiophenol, a thiazole, and a fluorine substituted phenyl ring. This ligand can be divided into a hydrophilic head group (carboxylate) and a hydrophobic tail (thiophenol, thiazole, phenyl). There is also a glycerol molecule in the structure, which is an artifact of the crystallization process and is not biologically relevant.
The ligand binding pocket (LBP) is made of (Arm I residues are green, Arm II residues are blue, Arm III residues are red), with fifteen residues that contact the ligand. interacts with the ligand through Phe246, Cys249, His287, Phe291, Ile327, His413, Leu433, and Tyr437. The of the ligand interacts via polar contacts with Arm I residues His287, His413, and Tyr437. , includes residues Val245, Val305, Val312, Leu317, and Ile 328, while includes Leu249 and Thr252. The of the ligand interacts via nonpolar contacts with residues from all three arms (Phe246, Phe291, His 413, Ile327, Leu433, Cys249, Val245, Val305, Val312, Leu317, Ile328, Thr252, and Leu294).
Comparing this structure to structures of ligand-bound PPARα and PPARγ, the authors found that from Arm II, Val312 and Ile328, are key to the specificity of this ligand for PPARδ.
Function
Activation of PPARδ improves overall metabolic health.
Disease
Relevance
