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Titolo:
Molecular modeling on kappa opioid receptor and its interaction with nonpeptide kappa opioid agonists
Autore:
Liu, DX; Jiang, HL; Shen, JS; Zhu, WL; Zhao, L; Chen, KX; Ji, RY;
Indirizzi:
Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China Chinese Acad Sci Shanghai Peoples R China 200031 200031, Peoples R China
Titolo Testata:
ACTA PHARMACOLOGICA SINICA
fascicolo: 2, volume: 20, anno: 1999,
pagine: 131 - 136
SICI:
0253-9756(199902)20:2<131:MMOKOR>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
BIOLOGICAL EVALUATION; AFFINITY; DOCKING;
Keywords:
molecular models; pharmaphore map; kappa opioid receptors; analgesics; ligands; cell surface receptors; structure-activity relationship; bacteriorhodopsin;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
9
Recensione:
Indirizzi per estratti:
Indirizzo: Chen, KX Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, PeoplesR China Chinese Acad Sci Shanghai Peoples R China 200031 eoples R China
Citazione:
D.X. Liu et al., "Molecular modeling on kappa opioid receptor and its interaction with nonpeptide kappa opioid agonists", ACT PHAR SI, 20(2), 1999, pp. 131-136

Abstract

AIM: To study the interaction between rc-opioid receptor and its nonpeptide agonists. METHODS: The "conservation patterns" for G-protein coupled receptors ( GPCR) were used to determine 7 transmembrane (TM) regions. Taking the crystallographic coordinates of bacteriorhodopsin (BR) as the template, the 3D structural model was constructed for 7 TM of kappa-opioid subtype with molecular mechanics (MM) method. Five highly active nonpeptide kappa-opioid agonists were docked into the 7 helices of kappa-opioid receptor to study the ligand-receptor interaction. RESULTS: Four important interactions between U-50488-like agonists and kappa-opioid receptors were drawn accordingto our modeling study: (I) the protonated pyrrolidine nitrogen of the ligands formed a hydrogen-bond with the carboxyl of Asp138; (2) the carbonyl oxygen of ligands forms a hydrogen bond to the hydroxyl Of Ser187; (3) the aryl groups connected to acylamide of the agonists inserted into a hydrophobic cavity enclosed by residues Val239, Val236, Phe235, Val232, Leu186, and Trp183; (4) the pyrrolidine of the ligands in the complexes was surrounded by Ile290, Asp138, Ile194, Ile135, and Cys131. CONCLUSION: The proposed interaction mechanism is helpful for further mutant experiments and designing novel potent kappa-opioid agonists.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/09/20 alle ore 11:28:05