Structural basis for recognition of diverse antidepressants by the human serotonin transporter

Jonathan A. Coleman, Eric Gouaux

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Selective serotonin reuptake inhibitors are clinically prescribed antidepressants that act by increasing the local concentrations of neurotransmitters at synapses and in extracellular spaces via blockade of the serotonin transporter. Here we report X-ray structures of engineered thermostable variants of the human serotonin transporter bound to the antidepressants sertraline, fluvoxamine, and paroxetine. The drugs prevent serotonin binding by occupying the central substrate-binding site and stabilizing the transporter in an outward-open conformation. These structures explain how residues within the central site orchestrate binding of chemically diverse inhibitors and mediate transporter drug selectivity.

Original languageEnglish (US)
Pages (from-to)170-175
Number of pages6
JournalNature Structural and Molecular Biology
Volume25
Issue number2
DOIs
StatePublished - Feb 1 2018

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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