Crystal structure of the PPAR-gamma ligand binding domain complexed with a novel partial agonist: a new region of the hydrophobic pocket could be exploited for drug design (Articolo in rivista)

Type

• Articolo in rivista (Classe)
• Prodotto della ricerca (Classe)

Label

• Crystal structure of the PPAR-gamma ligand binding domain complexed with a novel partial agonist: a new region of the hydrophobic pocket could be exploited for drug design (Articolo in rivista) (literal)

Anno

• 2008-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

• 10.1021/jm800733h (literal)

Alternative label

• Montanari R., Saccoccia F., Scotti E., Crestani M., Godio C., Gilardi F., Loiodice F., Fracchiolla G., Laghezza A., Tortorella P., Lavecchia A., Novellino E., Mazza F., Pochetti G. (2008)
  Crystal structure of the PPAR-gamma ligand binding domain complexed with a novel partial agonist: a new region of the hydrophobic pocket could be exploited for drug design
  in Journal of medicinal chemistry
  (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

• Montanari R., Saccoccia F., Scotti E., Crestani M., Godio C., Gilardi F., Loiodice F., Fracchiolla G., Laghezza A., Tortorella P., Lavecchia A., Novellino E., Mazza F., Pochetti G. (literal)

Pagina inizio

• 7768 (literal)

Pagina fine

• 7776 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

• 51 (literal)

Rivista

• Journal of medicinal chemistry (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali

• 9 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo

• 24 (literal)

Note

• ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

• Montanari R., Pochetti G., Saccoccia F. -IC-CNR, Roma Scotti E., Crestani M., Godio C., Gilardi F. - Università degli Studi di Milano Loiodice F., Fracchiolla G., Laghezza A., Tortorella P. - Università degli Studi di Bari Lavecchia A., Novellino E. - Università degli Studi di Napoli “Federico II” Mazza F., Aschi M. - Università di L'Aquila (literal)

Titolo

• Crystal structure of the PPAR-gamma ligand binding domain complexed with a novel partial agonist: a new region of the hydrophobic pocket could be exploited for drug design (literal)

Abstract

• The peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors regulating glucose and lipid metabolism. The search for new PPAR ligands with reduced adverse effects with respect to the marketed antidiabetic agents thiazolidinediones (TZDs) and the dual-agonists glitazars is highly desired. We report the crystal structure and activity of the two enantiomeric forms of a clofibric acid analogue, respectively complexed with the ligand-binding domain (LBD) of PPARg, and provide an explanation on molecular basis for their different potency and efficacy against PPARg. The more potent S-enantiomer is a dual PPARa/PPARg agonist which presents a partial agonism profile against PPARg. Docking of the S-enantiomer in the PPARa-LBD has been performed to explain its different subtype pharmacological profile. The hypothesis that partial agonists show differential stabilization of helix 3, when compared to full agonists, is also discussed. Moreover, the structure of the complex with the S-enantiomer reveals a new region of the PPARg-LBD never sampled before by other ligands. (literal)

Prodotto di

• Institute of Crystallography (IC) (Istituto)
• Studi strutturali e funzionali di proteine di interesse biomedico e biotecnologico (PM.P01.023.001) (Modulo)

Autore CNR

• ROBERTA MONTANARI (Unità di personale esterno)
• GIORGIO POCHETTI (Unità di personale interno)

Insieme di parole chiave

• Keywords of "Crystal structure of the PPAR-gamma ligand binding domain complexed with a novel partial agonist: a new region of the hydrophobic pocket could be exploited for drug design" (Insieme di parole chiave)

Incoming links:

Autore CNR di

• GIORGIO POCHETTI (Unità di personale interno)
• ROBERTA MONTANARI (Unità di personale esterno)

Prodotto

• Institute of Crystallography (IC) (Istituto)
• Studi strutturali e funzionali di proteine di interesse biomedico e biotecnologico (PM.P01.023.001) (Modulo)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi

• Journal of medicinal chemistry (Rivista)

Insieme di parole chiave di

• Keywords of "Crystal structure of the PPAR-gamma ligand binding domain complexed with a novel partial agonist: a new region of the hydrophobic pocket could be exploited for drug design" (Insieme di parole chiave)