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Crystal structure of the dopamine transporter in complex with a tricyclic antidepressant

The crystal structure of the dopamine transporter in complex with the tricyclic antidepressant nortriptyline could help guide the design of new antidepressants. Analysis of the crystal structure of the Drosophila dopamine transporter, which shares homology with the human transporter, in complex with Pamelor nortriptyline showed that the drug blocks substrate binding and locks the transporter in an outward-open conformation. The structure also revealed a binding site for cholesterol that helps stabilize the outward-open confirmation. Next steps could include using the structural information to rationally design new antidepressants.
Mallinckrodt plc markets Pamelor to treat depression.

SciBX 6(39); doi:10.1038/scibx.2013.1109
Published online Oct. 10, 2013

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Penmatsa, A. et al. Nature; published online Sept. 15, 2013;
doi:10.1038/nature12533
Contact: Eric Gouaux, Oregon Health & Science University, Portland, Ore.
e-mail:

gouauxe@ohsu.edu