Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Permeation and gating residues in serotonin transporter
Autore:
Chen, JG; Rudnick, G;
Indirizzi:
Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA Yale Univ NewHaven CT USA 06520 Dept Pharmacol, New Haven, CT 06520 USA
Titolo Testata:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
fascicolo: 3, volume: 97, anno: 2000,
pagine: 1044 - 1049
SICI:
0027-8424(20000201)97:3<1044:PAGRIS>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN DOPAMINE TRANSPORTER; NEUROTRANSMITTER TRANSPORTERS; ION DEPENDENCE; BINDING; ACCESSIBILITY; EXPRESSION; SUBSTRATE; FAMILIES; KINETICS; REVEALS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Rudnick, G Yale Univ, Sch Med, Dept Pharmacol, 333 Cedar St,POB 208066, New Haven, CT06520 USA Yale Univ 333 Cedar St,POB 208066 New Haven CT USA 06520 20 USA
Citazione:
J.G. Chen e G. Rudnick, "Permeation and gating residues in serotonin transporter", P NAS US, 97(3), 2000, pp. 1044-1049

Abstract

The third transmembrane domain (TM3) of serotonin transporter (SERT) contains two isoleucine residues previously proposed to be involved in binding and transport: of serotonin. When Ile-172 was replaced with cysteine, SERT became sensitive to inactivation by externally added [2-(trimethylammonium)ethyl]methanethio-sulfonate (MTSET). The disulfide product of this inactivation was not sensitive to reduction by externally added sulfhydryl compounds, but apparently reacted with intracellular reducing agents to spontaneously regenerate active SERT. The apparent accessibility of this residue to both external and cytoplasmic reagents is consistent with its localization near a serotonin binding site that is alternately exposed to both internal andexternal media. In another SERT mutant, I179C, transport also was inactivated by MTSET but substrate binding was resistant. External substrate bound to the inactivated I179C and enhanced its reactivation by free thiols, In norepinephrine transporter (NET), cysteine replacement of Ile-155 (corresponding to SERT Ile-179) also rendered the transporter sensitive to MTSET inactivation. In NET I155C, cocaine enhanced this inactivation, and the substrate, dopamine, apparently protected against inactivation. The characteristics of this protection suggest that dopamine was transported, converting NET to a form in which Ile-155 was occluded, The results support the proposal that TM3 of SERT and NET constitute part of the substrate permeation pathway, and that Ile-172 in SERT resides close to the substrate binding site. They also suggest that Ile-179 in SERT (and Ile-155 in NET) is in a conformationally sensitive part of TM3, which may act as part of an external gate.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 12:16:14