Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Molecular modelling of the ORL1 receptor and its complex with nociceptin
Autore:
Topham, CM; Mouledous, L; Poda, G; Maigret, B; Meunier, JC;
Indirizzi:
Inst077armacol & Biol Struct, CNRS UPR 9062, Unite Neuropharmacol Mol, F-31 Inst Pharmacol & Biol Struct Toulouse France 4 Neuropharmacol Mol, F-31 Univ Nancy 1, Chim Theor Lab, F-54506 Vandoeuvre Nancy, France Univ Nancy 1 Vandoeuvre Nancy France F-54506 06 Vandoeuvre Nancy, France
Titolo Testata:
PROTEIN ENGINEERING
fascicolo: 12, volume: 11, anno: 1998,
pagine: 1163 - 1179
SICI:
0269-2139(199812)11:12<1163:MMOTOR>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
KAPPA-OPIOID RECEPTOR; PROTEIN-COUPLED RECEPTORS; SITE-DIRECTED MUTAGENESIS; TACHYKININ NK-1 RECEPTOR; AFFINITY AGONIST BINDING; ACID SUBSTITUTION TABLES; MU-OPIATE RECEPTOR; ORPHANIN-FQ; AMINO-ACIDS; HOMOLOGOUS PROTEINS;
Keywords:
molecular modelling; G-protein coupled receptor; opioid receptor like 1 (ORL1) receptor; neuropeptide; nociceptin; structure-activity relationships;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
110
Recensione:
Indirizzi per estratti:
Indirizzo: Topham, CM InstRoutemacol & Biol Struct, CNRS UPR 9062, Unite Neuropharmacol Mol, 205 Inst Pharmacol & Biol Struct 205 Route Narbonne Toulouse France 4
Citazione:
C.M. Topham et al., "Molecular modelling of the ORL1 receptor and its complex with nociceptin", PROTEIN ENG, 11(12), 1998, pp. 1163-1179

Abstract

The opioid receptor like (ORL1) receptor is a G-protein coupled receptor superfamily, and regulates a plethora of neurophysiological functions. The structural requirements for receptor activation by its endogenous agonist, nociceptin (FGGFTGARKSARKLANQ), differ markedly from those of the kappa-opioid receptor and its putative peptide agonist, dynorphin A (YGGFLRRIRPKLKWDNQ). In order to probe the functional architecture of the ORL1 receptor, a molecular model of the receptor has been built, including the TR I domain and the extra- and intracellular loops. An extended binding site able to accommodate nociceptin(1-13), the shortest fully active analogue of nociceptin,has been characterized. The N-terminal FGGF tetrapeptide is proposed to bind in a highly conserved region, comprising tno distinct hydrophobic pockets in a cavity formed by TM helices 3, 5, 6 and 7, capped by the acidic second extracellular (EL2) loop controlling access to the TM elements of the peptide binding site. The nociceptin conformation provides for the selective preference of the ORL1 receptor for nociceptin over dynorphin A, conferred by residue positions 5 and 6 (TG versus LR), and the favourable interactionof its highly positively charged core (residues 8-13) with the EL2 loop, thought to mediate receptor activation. The functional roles of the EL2 loopand the conserved N-terminal tetrapeptide opioid 'message' binding site are discussed in the context of the different structural requirements of the ORL1 and kappa-opioid receptors for activation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/10/20 alle ore 00:29:42