@article{70f214d65e144cf79e68ade0624e1088,
title = "Neurotransmitter and psychostimulant recognition by the dopamine transporter",
abstract = "Na+/Cl--coupled biogenic amine transporters are the primary targets of therapeutic and abused drugs, ranging from antidepressants to the psychostimulants cocaine and amphetamines, and to their cognate substrates. Here we determine X-ray crystal structures of the Drosophila melanogaster dopamine transporter (dDAT) bound to its substrate dopamine, a substrate analogue 3,4-dichlorophenethylamine, the psychostimulants d-amphetamine and methamphetamine, or to cocaine and cocaine analogues. All ligands bind to the central binding site, located approximately halfway across the membrane bilayer, in close proximity to bound sodium and chloride ions. The central binding site recognizes three chemically distinct classes of ligands via conformational changes that accommodate varying sizes and shapes, thus illustrating molecular principles that distinguish substrates from inhibitors in biogenic amine transporters.",
author = "Wang, {Kevin H.} and Aravind Penmatsa and Eric Gouaux",
note = "Funding Information: Acknowledgements We thank J. Coleman, C.-H. Lee, S. Mansoor and other Gouaux laboratory members for helpful discussions, L. Vaskalis for assistance with figures and H. Owen for help with manuscript preparation. We acknowledge the staff of the Berkeley Center for Structural Biology at the Advanced Light Source and the NortheasternCollaborative Access TeamattheAdvancedPhotonSource for assistance with data collection. This work was supported by an NIMH Ruth Kirschstein postdoctoral fellowship and Brain and Behavior Research Foundation Young Investigator research award (K.H.W.), a postdoctoral fellowship from the American Heart Association (A.P.) and by the NIH (E.G) and the Methamphetamine Abuse Research Center of OHSU (P50DA018165 to E.G). E.G. is an investigator with the Howard Hughes Medical Institute. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited. All rights reserved.",
year = "2015",
month = may,
day = "21",
doi = "10.1038/nature14431",
language = "English (US)",
volume = "521",
pages = "322--327",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7552",
}