Antidepressant binding site in a bacterial homologue of neurotransmitter transporters

Satinder K. Singh, Atsuko Yamashita and Eric Gouaux ()
Additional contact information
Satinder K. Singh: The Vollum Institute and,
Atsuko Yamashita: Columbia University, 650 West 168th Street, New York, New York 10032, USA
Eric Gouaux: The Vollum Institute and,

Nature, 2007, vol. 448, issue 7156, 952-956

Abstract: Antidepressant design Tricyclic antidepressants act by inhibiting sodium-coupled neurotransmitter transporters in the brain, yet little is known about how these inhibitors work at the molecular level. The LeuT leucine transporter from the thermophilic bacterium Aquifex aeolicus is a homologue of the neurotransmitter transporters, and so far the only one that has proved amenable to structural analysis. Singh et al. therefore studied the mechanism of binding of three antidepressants — clomipramine, desipramine and imipramine — to LeuT. The drugs bind noncompetitively to an extracellular facing vestibule to inhibit substrate release. Although the norepinephrine and serotonin receptors in the human brain differ markedly from LeuT, this work has pinpointed an additional region that might be exploited for the development of new inhibitors with therapeutic potential.

Date: 2007
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/nature06038 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:448:y:2007:i:7156:d:10.1038_nature06038

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature06038

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().