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Titolo:
Three-dimensional models of glutamate receptors
Autore:
Sutcliffe, MJ; Smeeton, AH; Wo, ZG; Oswald, RE;
Indirizzi:
Univ Leicester, Dept Chem, Leicester LE1 7RH, Leics, England Univ Leicester Leicester Leics England LE1 7RH er LE1 7RH, Leics, England Cornell Univ, Coll Vet Med, Dept Pharmacol, Ithaca, NY 14853 USA Cornell Univ Ithaca NY USA 14853 ed, Dept Pharmacol, Ithaca, NY 14853 USA
Titolo Testata:
Faraday discussions
fascicolo: 111, , anno: 1998,
pagine: 259 - 272
SICI:
1359-6640(1998):111<259:TMOGR>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
D-ASPARTATE RECEPTOR; MULTIPLE SEQUENCE ALIGNMENTS; HISTIDINE-BINDING PROTEIN; GATED ION CHANNELS; NMDA RECEPTOR; SELECTIVITY FILTER; POTASSIUM CHANNEL; ACID RECEPTORS; LIGAND-BINDING; 3-DIMENSIONAL MODELS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Physical, Chemical & Earth Sciences
Citazioni:
67
Recensione:
Indirizzi per estratti:
Indirizzo: Sutcliffe, MJ Univ Leicester, Dept Chem, Leicester LE1 7RH, Leics, EnglandUniv Leicester Leicester Leics England LE1 7RH ics, England
Citazione:
M.J. Sutcliffe et al., "Three-dimensional models of glutamate receptors", FARADAY DIS, (111), 1998, pp. 259-272

Abstract

Structural models of glutamate receptors have been produced as part of a multidisciplinary study of neuronal function-both ligand/receptor interactions and ion transport-at the atomic level. The models have concentrated on the agonist binding and transmembrane domains of ionotropic (i.e. ligand-gated) glutamate receptors (iGluRs), and have aided our understanding of the molecular determinants of (1) ligand binding and (2) channel activity. The model building process involved a combination of homology modelling, distance geometry, molecular mechanics, protein-ligand and protein-protein docking, electrostatic calculations and manual adjustment, in conjunction with restraints from site-directed mutagenesis, ligand binding and electrophysiological studies. The initial models were used to produce hypotheses which weretested experimentally; these models have been subsequently refined as partof an extremely effective multidisciplinary study using an iterative molecular modelling/experimental verification cycle in which restraints derived from experimental studies are used at all stages, and the findings from oneround of modelling are used as restraints in the next. By studying a variety of agonists and antagonists, details have been built up of (1) those residues involved in ligand binding and (2) the role of agonist binding (i.e. agonist-induced conformational change) in channel gating. The models also aid our understanding of the conductance properties of the channels.

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Documento generato il 25/11/20 alle ore 06:46:06