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

Publication Type:

Journal Article

Authors:

Penmatsa, Aravind; Wang, Kevin H; Gouaux, Eric

Source:

Nat Struct Mol Biol, Volume 22, Issue 6, p.506-508 (2015)

Keywords:

Animals, Antidepressive Agents, Crystallography, X-Ray, Dopamine Plasma Membrane Transport Proteins, Drosophila melanogaster, Drosophila Proteins, Fluoxetine, Morpholines, Protein Binding, Reboxetine

Abstract:

<p>Most antidepressants elicit their therapeutic benefits through selective blockade of Na(+)/Cl(-)-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. </p>

PDB: 
4XNU 4XNX
Detector: 
PILATUS
Beamline: 
24-ID-C