1NYX

Ligand binding domain of the human peroxisome proliferator activated receptor gamma in complex with an agonist

Summary for 1NYX

• Entry DOI: 10.2210/pdb1nyx/pdb
• Related: 1KNU
• Descriptor: peroxisome proliferator activated receptor gamma, (2S)-2-ETHOXY-3-{4-[2-(10H-PHENOXAZIN-10-YL)ETHOXY]PHENYL}PROPANOIC ACID (3 entities in total)
• Functional Keywords: ppar, nuclear receptor, transcription, gene regulation, agonist complex
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P37231
• Total number of polymer chains: 2
• Total formula weight: 63548.69

Authors

Ebdrup, S.,Pettersson, I.,Rasmussen, H.B.,Deussen, H.-J.,Frost Jensen, A.,Mortensen, S.B.,Fleckner, J.,Pridal, L.,Nygaard, L.,Sauerberg, P. (deposition date: 2003-02-14, release date: 2003-07-15, Last modification date: 2024-03-13)

Primary citation

Ebdrup, S.,Pettersson, I.,Rasmussen, H.B.,Deussen, H.-J.,Frost Jensen, A.,Mortensen, S.B.,Fleckner, J.,Pridal, L.,Nygaard, L.,Sauerberg, P.
Synthesis and biological and structural characterization of the dual-acting peroxisome proliferator-activated receptor alpha/gamma agonist ragaglitazar
J.MED.CHEM., 46:1306-1317, 2003

PubMed Abstract: A new and improved synthesis of the peroxisome proliferator-activated receptor (PPAR) agonist ragaglitazar applicable for large-scale preparation has been developed. The convergent synthetic procedure was based on a novel enzymatic kinetic resolution step. The conformation of ragaglitazar bound to the hPPARgamma receptor was quite different compared to the single-crystal structures of the l-arginine salt of ragaglitazar. In particular, the phenoxazine ring system had varying orientations. Ragaglitazar had high affinity for the hPPARalpha and -gamma receptors with IC(50) values of 0.98 and 0.092 microM, respectively. The lack of hPPARdelta activity could be explained by the absence of binding in the tail-up pocket in the hPPARdelta receptor, in contrast to the hPPARdelta agonist GW2433, which was able to bind in both the tail-up and tail-down pockets of the receptor.

PubMed: 12672231
DOI: 10.1021/jm021027r

Experimental method

X-RAY DIFFRACTION (2.65 Å)