Structure/function relationships in serotonin transporter: new insights from the structure of a bacterial transporter

Handb Exp Pharmacol. 2006:(175):59-73. doi: 10.1007/3-540-29784-7_3.

Abstract

Serotonin transporter (SERT) serves the important function of taking up serotonin (5-HT) released during serotonergic neurotransmission. It is the target for important therapeutic drugs and psychostimulants. SERT catalyzes the influx of 5-HT together with Na+ and Cl- in a 1:1:1 stoichiometry. In the same catalytic cycle, there is coupled efflux of one K+ ion. SERT is one member of a large family of amino acid and amine transporters that is believed to utilize similar mechanisms of transport. A bacterial member of this family was recently crystallized, revealing the structural basis of these transporters. In light of the new structure, previous results with SERT have been re-interpreted, providing new insight into the substrate binding site, the permeation pathway, and the conformational changes that occur during the transport cycle.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Binding Sites
  • Biological Transport
  • Humans
  • Molecular Sequence Data
  • Protein Binding
  • Protein Conformation
  • Serotonin / metabolism*
  • Serotonin Plasma Membrane Transport Proteins / chemistry
  • Serotonin Plasma Membrane Transport Proteins / metabolism*
  • Structure-Activity Relationship

Substances

  • Bacterial Proteins
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin