A putative model of the dopamine transporter

doi:10.1016/0169-328X(94)90009-4

Molecular Brain Research

Volume 27, Issue 2, December 1994, Pages 265-274

https://doi.org/10.1016/0169-328X(94)90009-4 Get rights and content

Abstract

A three-dimensional model of the human dopamine transporter was constructed by molecular modeling techniques from its amino acid sequence, based on sequence analysis of this and 9 other transporter proteins. The model has 12 membrane spanning α-helices arranged in two 7-helical bundles, loops between helices and amino- and carboxy termini. The molecular electrostatic potentials were mainly negative at the synaptic side and positive in the cytoplasmic domains of the transporter model, strongly positive in some of the transmembrane domains, and strongly negative in other transmembrane domains. The model suggests specific binding sites for dopamine and cocaine, a functional role for chloride ions, and accounts for known structure-activity relationships of cocaine analogs at the dopamine transporter.

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Research reportA putative model of the dopamine transporter

Abstract

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Systematic analysis of structural data as a research technique in organic chemistry

Acc. Chem. Res.

Cloning and expression of a functional serotonin transporter from rat brain

Nature

Cocaine receptor: biochemical characterization and structure activity relationships of cocaine analogues at the dopamine transporter

J. Med. Chem.

Construction and molecular modeling of phospholipid surfaces

J. Comput. Chem.

Empirical predictions of protein conformation

Annu. Rev. Biochem.

A single point mutation (Phe340- > Leu340) of a conserved phenylalanine abolished 4-[125]iodo-(2,5-dimethoxy)phenylisopropylamine and [3H]-mesulergine but not [3H]-ketanserin binding to 5-hydroxytryptamine2 receptors

Mol. Pharmacol.

Molecular dynamics of dopamine at the dopamine D2 receptor

A comprehensive set of sequence analysis programs for the VAX

Nucl. Acid. Res.

Molecular modelling of drugs, neurotransmitters and receptors in the central nervous system

Molecular dynamics and electrostatic potentials of dopamine

Mol. Neuropharmacol.

Three-dimensional structure of membrane and surface proteins

Annu. Rev. Biochem.

Research report
A putative model of the dopamine transporter

A single point mutation (Phe³⁴⁰- > Leu³⁴⁰) of a conserved phenylalanine abolished 4-[¹²⁵]iodo-(2,5-dimethoxy)phenylisopropylamine and [³H]-mesulergine but not [³H]-ketanserin binding to 5-hydroxytryptamine₂ receptors