X-ray structures of Drosophila dopamine transporter in complex with nisoxetine and reboxetine

Aravind Penmatsa, Kevin H. Wang, Eric Gouaux

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Most antidepressants elicit their therapeutic benefits through selective blockade of Na + /Cl â -coupled neurotransmitter transporters. Here we report X-ray structures of the Drosophila melanogaster dopamine transporter in complexes with the polycyclic antidepressants nisoxetine or reboxetine. The inhibitors stabilize the transporter in an outward-open conformation by occupying the substrate-binding site. These structures explain how interactions between the binding pocket and substituents on the aromatic rings of antidepressants modulate drug-transporter selectivity.

Original languageEnglish (US)
Pages (from-to)506-508
Number of pages3
JournalNature Structural and Molecular Biology
Volume22
Issue number6
DOIs
StatePublished - Jun 3 2015

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nisoxetine
Dopamine Plasma Membrane Transport Proteins
Antidepressive Agents
Drosophila
X-Rays
Neurotransmitter Transport Proteins
Drosophila melanogaster
Binding Sites
reboxetine

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology
  • Medicine(all)

Cite this

X-ray structures of Drosophila dopamine transporter in complex with nisoxetine and reboxetine. / Penmatsa, Aravind; Wang, Kevin H.; Gouaux, Eric.

In: Nature Structural and Molecular Biology, Vol. 22, No. 6, 03.06.2015, p. 506-508.

Research output: Contribution to journalArticle

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