title: Homology modeling of the serotonin transporter: insights into the primary escitalopram-binding site.
abstract: 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.
authors.affiliation: MEMPHYS-Center for Biomembrane Physics, Department of Chemistry, Technical University of Denmark, Building 206, 2800 Kgs. Lyngby, Denmark.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Jørgensen
authors.forename: Lena
authors.initials: L
authors.lastname: Tagmose
authors.forename: Anne Marie M
authors.initials: AM
authors.lastname: Jørgensen
authors.forename: Sid
authors.initials: S
authors.lastname: Topiol
authors.forename: Michael
authors.initials: M
authors.lastname: Sabio
authors.forename: Klaus
authors.initials: K
authors.lastname: Gundertofte
authors.forename: Klaus P
authors.initials: KP
authors.lastname: Bøgesø
authors.forename: Günther H
authors.initials: GH
authors.lastname: Peters
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015283:Citalopram / Q000737:chemistry* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007930:Leucine / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D050486:Serotonin Plasma Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism*; D012964:Sodium / Q000737:chemistry / Q000378:metabolism; D040681:Structural Homology, Protein
chemical_list: D029968:Escherichia coli Proteins; D008024:Ligands; D050486:Serotonin Plasma Membrane Transport Proteins; D015283:Citalopram; D012964:Sodium; D007930:Leucine