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 language | English (US) |
|---|---|
| Pages (from-to) | 506-508 |
| Number of pages | 3 |
| Journal | Nature Structural and Molecular Biology |
| Volume | 22 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 3 2015 |
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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 journal › Article
}
TY - JOUR
T1 - X-ray structures of Drosophila dopamine transporter in complex with nisoxetine and reboxetine
AU - Penmatsa, Aravind
AU - Wang, Kevin H.
AU - Gouaux, Eric
PY - 2015/6/3
Y1 - 2015/6/3
N2 - 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.
AB - 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.
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U2 - 10.1038/nsmb.3029
DO - 10.1038/nsmb.3029
M3 - Article
C2 - 25961798
AN - SCOPUS:84930414357
VL - 22
SP - 506
EP - 508
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
SN - 1545-9993
IS - 6
ER -