Steric hindrance mutagenesis in the conserved extracellular vestibule impedes allosteric binding of antidepressants to the serotonin transporter

Per Plenge, Lei Shi, Thijs Beuming, Jerez Te, Amy Hauck Newman, Harel Weinstein, Ulrik Gether, Claus J Loland

65 Citationer (Scopus)

Abstract

Background: The serotonin transporter contains an allosteric binding site with unknown location. Results: We use molecular modeling, mutagenesis, and zinc site engineering to locate and inhibit the allosteric binding site. Conclusion: Data are consistent with the allosteric binding site being located in the extracellular vestibule. Significance: This opens the search for a new generation of antidepressant drugs directed toward the proposed allosteric binding site.

OriginalsprogEngelsk
TidsskriftThe Journal of Biological Chemistry
Vol/bind287
Udgave nummer47
Sider (fra-til)39316-26
Antal sider11
ISSN0021-9258
DOI
StatusUdgivet - 16 nov. 2012

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