Homology modeling of the serotonin transporter: insights into the primary escitalopram-binding site

ChemMedChem. 2007 Jun;2(6):815-26. doi: 10.1002/cmdc.200600242.


The serotonin transporter (SERT) is one of the neurotransmitter transporters that plays a critical role in the regulation of endogenous amine concentrations and therefore is an important target for therapeutic agents affecting the central nervous system. The recently published, high resolution X-ray structure of the closely related amino acid transporter, Aquifex aeolicus leucine transporter (LeuT), provides an opportunity to develop a three-dimensional model of the structure of SERT. We present herein a homology model of SERT using LeuT as the template and containing escitalopram as a bound ligand. Our model explains selectivities known from mutational studies and varying ligand data, which are discussed and illustrated in the paper.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Citalopram / chemistry*
  • Citalopram / metabolism*
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / metabolism
  • Humans
  • Leucine / chemistry
  • Ligands
  • Models, Molecular*
  • Molecular Sequence Data
  • Protein Binding
  • Sequence Homology, Amino Acid
  • Serotonin Plasma Membrane Transport Proteins / chemistry*
  • Serotonin Plasma Membrane Transport Proteins / metabolism*
  • Sodium / chemistry
  • Sodium / metabolism
  • Structural Homology, Protein*


  • Escherichia coli Proteins
  • Ligands
  • Serotonin Plasma Membrane Transport Proteins
  • Citalopram
  • Sodium
  • Leucine