Related Experiment Video
Updated: Aug 9, 2026

Thermostabilization, Expression, Purification, and Crystallization of the Human Serotonin Transporter Bound to S-citalopram
Published on: November 27, 2016
Conserved serine residues in serotonin transporter contribute to high-affinity cocaine binding
Howard H Gu1, Xiaohong Wu, Dawn D Han
1Department of Pharmacology, The Ohio State University College of Medicine, 333 West 10th Avenue, Columbus, OH 43210, USA. gu.37@osu.edu
Abstract:
Serotonin transporter (SERT) is one of the key protein targets of cocaine. Despite intensive studies, it is not clear where cocaine binds to its targets and what residues are involved in cocaine binding. We have cloned the serotonin transporter from silkworm (Bombyx mori, bmSERT). When expressed in cultured cells, bmSERT is over 20-fold less sensitive to cocaine than Drosophila melanogaster SERT (dmSERT). We performed species-scanning mutagenesis using bmSERT and dmSERT. There are two adjacent threonine residues in transmembrane domain 12 of bmSERT where the corresponding residues are two serines in dmSERT and in all known mammalian monoamine transporters. Replacing the serine residues with threonines in dmSERT reduces cocaine sensitivity; while switching the two threonine residues in bmSERT to serines increased cocaine sensitivity. Mutations at the corresponding residues in dopamine transporter also changed cocaine affinity. Our results suggest that the conserved serine residues in SERT contribute to high-affinity cocaine binding.
Related Concept Videos
Drugs Affecting Neurotransmitter Release or Uptake
Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists
Adrenergic Agonists: Indirect-Acting Agents
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral bioavailability, and...
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters
G-protein Coupled Receptors
Conserved Binding Sites
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...

