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Titolo:
Molecular dynamics of NPYY1 receptor activation
Autore:
Sylte, I; Andrianjara, CR; Calvet, A; Pascal, Y; Dahl, SG;
Indirizzi:
Univ Tromso, Fac Med, Dept Pharmacol, N-9037 Tromso, Norway Univ Tromso Tromso Norway N-9037 , Dept Pharmacol, N-9037 Tromso, Norway Inst Rech Jouveinal Parke Davies, F-94265 Fresnes, France Inst Rech Jouveinal Parke Davies Fresnes France F-94265 Fresnes, France
Titolo Testata:
BIOORGANIC & MEDICINAL CHEMISTRY
fascicolo: 12, volume: 7, anno: 1999,
pagine: 2737 - 2748
SICI:
0968-0896(199912)7:12<2737:MDONRA>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
NEUROPEPTIDE-Y RECEPTOR; PROTEIN-COUPLED RECEPTORS; TACHYKININ NK-1 RECEPTOR; KAPPA-OPIOID RECEPTOR; LIGAND-BINDING SITE; PANCREATIC-POLYPEPTIDE; FUNCTIONAL EXPRESSION; HIGH-AFFINITY; Y-1 RECEPTOR; PEPTIDE-YY;
Keywords:
NPYY1-receptor; ligand interactions; molecular dynamics; receptor activation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
62
Recensione:
Indirizzi per estratti:
Indirizzo: Sylte, I Univ Tromso, Fac Med, Dept Pharmacol, N-9037 Tromso, Norway Univ Tromso Tromso Norway N-9037 armacol, N-9037 Tromso, Norway
Citazione:
I. Sylte et al., "Molecular dynamics of NPYY1 receptor activation", BIO MED CH, 7(12), 1999, pp. 2737-2748

Abstract

A three-dimensional model of the human neuropeptide Y(NPY)Y-1 receptor (hY(1)) was constructed, energy refined and used to simulate molecular receptor interactions of the peptide ligands NPY, [L31, P34]NPY, peptide YY (PYY) and pancreatic polypeptide (PP), and of the nonpeptide antagonist R-N-2-(diphenylacetyl)-N-(4-hydroxyphenyl)methyl-argininamide (BIBP3226) and its S-enantiomer BIBP3435. The best complementarity in charges between the receptor and the peptides, and the best structural accordance with experimental studies, was obtained with amino acid 1-4 of the peptides interacting with Asp194, Asp200, Gln201, Phe202 and Trp288 in the receptor. Arg33 and Arg35 ofthe peptides formed salt bridges with Asp104 and Asp287, respectively, while Tyr36 interacted in a binding pocket formed by Phe41, Thr42, Tyr100, Asn297, His298 and Phe302. Calculated electrostatic potentials around NPY and hY(1) molecules indicated that ligand binding is initiated by electrostaticinteractions between a highly positive region in the N- and C-terminal parts of the peptides, and a negative region in the extracellular receptor domains. Molecular dynamics simulations of NPY and BIBP3226 interactions with the receptor indicated rigid body motions of TMH5 and TMH6 upon NPY bindingas mechanisms of receptor activation, and that BIBP3226 may act as an antagonist by constraining these motions. (C) 1999 Elsevier Science Ltd. All rights reserved.

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Documento generato il 28/11/20 alle ore 00:55:39