Interaction between peroxisome proliferator-activated receptor gamma and its agonists: docking study of oximes having 5-benzyl-2,4-thiazolidinedione.
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Iwata Y, Miyamoto S, Takamura M, Yanagisawa H, Kasuya A
Interaction between peroxisome proliferator-activated receptor gamma and its agonists: docking study of oximes having 5-benzyl-2,4-thiazolidinedione.
J Mol Graph Model. 2001;19(6):536-42, 598-600.
- PubMed ID
- 11552681 [ View in PubMed]
- Abstract
The molecular modelling of oximes having 5-benzyl-2,4-thiazolidinedione moieties, agonists of the peroxisome proliferator-activated receptor gamma (PPAR gamma), was performed with respect to their structures complexed with the ligand binding domain of PPAR gamma. For each ligand molecule, the 5-benzyl-2,4-thiazolidinedione head group was used as an anchor and the conformation of the rest of the molecule was searched for the most energetically favorable interaction with the receptor by systematic conformation search and manual modelling. Although both tail-up and tail-down configurations, which have been observed in the crystal structure of eicosapentaenoic acid when complexed with PPAR delta, appeared among the lowest energy structures for most of the compounds, potent agonists were found to adopt a configuration similar to that of rosiglitazone when bound to PPAR gamma, according to the crystal structure. The structure-activity relationships were analyzed based on the receptor-ligand interaction. The alkyl group and the aromatic ring of the tail group of the ligands had hydrophobic interactions with the receptor, and these interactions were found to be essential for the strong activity.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Icosapent Peroxisome proliferator-activated receptor delta Protein Humans YesAgonistDetails Icosapent Peroxisome proliferator-activated receptor gamma Protein Humans YesAgonistRegulatorDetails