Molecular modeling of the GABA/GABAB receptor complex

被引：14

作者：

Bernard, P

Guedin, D

Hibert, H

机构：

[1] Fac Pharm, UMR CNRS ULP 7081, Lab Pharmacochim Commun Cellulaire, F-67400 Illkirch Graffenstaden, France

[2] Hoechst Marion Roussel, F-92235 Romainville, France

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2001年 / 44卷 / 01期

关键词：

D O I：

10.1021/jm000915o

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A three-dimensional model of the extracellular domain of the GABAB receptor has been built by homology with the leucine/isoleucine/valine-binding protein. The complete putative GABA-binding site in the extracellular domain is described in both the open and closed states. The dynamics of the "Venus flytrap" mechanism has been studied, suggesting that the molecular dipole moments play a key role in GABA binding and receptor activation. Important residues putatively implicated either in ligand binding or in the dynamics of the receptor are pinpointed, thus highlighting target residues for mutagenesis experiments and model validation.

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页码：27 / 35

页数：9

相关论文

共 42 条

[1] Automated docking of 82 N-benzylpiperidine derivatives to mouse acetylcholinesterase and comparative molecular field analysis with 'natural' alignment [J].

Bernard, P ;

Kireev, DB ;

Chrétien, JR ;

Fortier, PL ;

Coppet, L .

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 1999, 13 (04) :355-371

[2]

BOWERY NG, 1992, ARZNEIMITTELFORSCH, V42-1, P215

[3] [H-3] (-)BACLOFEN - AN IMPROVED LIGAND FOR GABAB SITES [J].

BOWERY, NG ;

HILL, DR ;

HUDSON, AL .

NEUROPHARMACOLOGY, 1985, 24 (03) :207-210

[4] The agonist-binding domain of the calcium-sensing receptor is located at the amino-terminal domain [J].

Bräuner-Osborne, H ;

Jensen, AA ;

Sheppard, PO ;

O'Hara, P ;

Krogsgaard-Larsen, P .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (26) :18382-18386

[5] CLONING AND CHARACTERIZATION OF AN EXTRACELLULAR CA2+-SENSING RECEPTOR FROM BOVINE PARATHYROID [J].

BROWN, EM ;

GAMBA, G ;

RICCARDI, D ;

LOMBARDI, M ;

BUTTERS, R ;

KIFOR, O ;

SUN, A ;

HEDIGER, MA ;

LYTTON, J ;

HEBERT, SC .

NATURE, 1993, 366 (6455) :575-580

[6] The role of GABA(B) mechanisms in animal models of absence seizures [J].

Caddick, SJ ;

Hosford, DA .

MOLECULAR NEUROBIOLOGY, 1996, 13 (01) :23-32

[7] Pharmacology and functions of metabotropic glutamate receptors [J].

Conn, PJ ;

Pin, JP .

ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 1997, 37 :205-237

[8] Pharmacophore models of group I and group II metabotropic glutamate receptor agonists. Analysis of conformational, steric, and topological parameters affecting potency and selectivity [J].

Costantino, G ;

Macchiarulo, A ;

Pellicciari, R .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (15) :2816-2827

[9] Homology modeling of metabotropic glutamate receptors. (mGluRs) structural motifs affecting binding modes and pharmacological profile of mGluR1 agonists and competitive antagonists [J].

Costantino, G ;

Pellicciari, R .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (20) :3998-4006

[10]

Enna S. J., 1997, GABA RECEPTORS

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