Thursday, October 10, 2013
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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
Mallinckrodt plc markets
Pamelor to treat depression.
Published online Oct. 10, 2013
Patent and licensing status
Penmatsa, A. et al.
Nature; published online Sept. 15, 2013;
Contact: Eric Gouaux, Oregon Health & Science
University, Portland, Ore.
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