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Article Abstract
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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608549 | PMC |
| http://dx.doi.org/10.1038/nsmb.3029 | DOI Listing |
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