Structural Insight into Peroxisome Proliferator-Activated Receptor ³ Binding of Two Ureidofibrate-Like Enantiomers by Molecular Dynamics, Cofactor Interaction Analysis, and Site-Directed Mutagenesis (Articolo in rivista)

Type

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

Label

• Structural Insight into Peroxisome Proliferator-Activated Receptor ³ Binding of Two Ureidofibrate-Like Enantiomers by Molecular Dynamics, Cofactor Interaction Analysis, and Site-Directed Mutagenesis (Articolo in rivista) (literal)

Anno

• 2010-01-01T00:00:00+01:00 (literal)

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

• 10.1021/jm9013899 (literal)

Alternative label

• G. Pochetti (a), N. Mitro (b,c), A. Lavecchia (d), F. Gilardi (b,h), N. Besker (e), E. Scotti (b,i), M. Aschi (f), N. Re (e), G. Fracchiolla (g), A. Laghezza (g), P. Tortorella (g), R. Montanari (a), E. Novellino (d), F. Mazza (a,l), M. Crestani (b) and F. Loiodice (g) (2010)
  Structural Insight into Peroxisome Proliferator-Activated Receptor ³ Binding of Two Ureidofibrate-Like Enantiomers by Molecular Dynamics, Cofactor Interaction Analysis, and Site-Directed Mutagenesis
  in Journal of medicinal chemistry
  (literal)

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

• G. Pochetti (a), N. Mitro (b,c), A. Lavecchia (d), F. Gilardi (b,h), N. Besker (e), E. Scotti (b,i), M. Aschi (f), N. Re (e), G. Fracchiolla (g), A. Laghezza (g), P. Tortorella (g), R. Montanari (a), E. Novellino (d), F. Mazza (a,l), M. Crestani (b) and F. Loiodice (g) (literal)

Pagina inizio

• 4354 (literal)

Pagina fine

• 4366 (literal)

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

• 53 (literal)

Rivista

• Journal of medicinal chemistry (Rivista)

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

• 13 (literal)

Note

• ISI Web of Science (WOS) (literal)

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

• a) Istituto di Cristallografia, Consiglio Nazionale delle Ricerche, Montelibretti, 00015 Monterotondo Stazione, Roma, Italia; b) Laboratorio \"Giovanni Galli\" di Biochimica e Biologia Molecolare dei Lipidi e Spettrometria di Massa; c) Laboratorio \"Giovanni Armenise-Harvard Foundation\", Dipartimento di Scienze Farmacologiche, Università degli Studi di Milano, 20133 Milano, Italia; d) Dipartimento di Chimica Farmaceutica e Tossicologica, Università degli Studi di Napoli \"Federico II\", 80131 Napoli, Italia; e) Dipartimento di Scienze del Farmaco, Universit?à \"G. D'Annunzio\", 06100 Chieti, Italia; f) Dipartimento di Chimica, Ingegneria Chimica e Materiali, Università di L'Aquila, 67010 L'Aquila, Italia; g) Dipartimento Farmaco-Chimico, Università degli Studi di Bari \"Aldo Moro\", 70126 Bari, Italia; h) Current address: University of Lausanne, Center for Integrative Genomics, Genopode Building, Room 5010, 1015 Lausanne, Switzerland; i) Current address: Department of Pathology and Laboratory Medicine/Howard Hughes Medical Institutes, University of California at Los Angeles, Los Angeles, California; l) Dipartimento di Scienze della Salute, Università di L'Aquila, 67010 L'Aquila, Italia; (literal)

Titolo

• Structural Insight into Peroxisome Proliferator-Activated Receptor ³ Binding of Two Ureidofibrate-Like Enantiomers by Molecular Dynamics, Cofactor Interaction Analysis, and Site-Directed Mutagenesis (literal)

Abstract

• Molecular dynamics simulations were performed on two ureidofibrate-like enantiomers to gain insight into their different potency and efficacy against PPAR³. The partial agonism of the S enantiomer seems to be due to its capability to stabilize different regions of the receptor allowing the interaction with both coactivators and corepressors as shown by fluorescence resonance energy transfer (FRET) assays. The recruitment of the corepressor N-CoR1 by the S enantiomer on two different responsive elements of PPAR³ regulated promoters was confirmed by chromatin immunoprecipitation assays. Cell-based transcription assays show that PPAR³ coactivator 1± (PGC-1±) and cAMP response element binding protein-binding protein (CBP) enhance the basal and ligand-stimulated receptor activity acting as coactivators of PPAR³, whereas the receptor interacting protein 140 (RIP140) and the nuclear corepressor 1 (N-CoR1) repress the transcriptional activity of PPAR³. We also tested the importance of the residue Q286 on the transcriptional activity of the receptor by site-directed mutagenesis and confirmed its key role in the stabilization of helix 12. Molecular modeling studies were performed to provide a molecular explanation for the different behavior of the mutants. (literal)

Prodotto di

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

Autore CNR

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

Incoming links:

Autore CNR di

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

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)