6awn | pdb_00006awn
X-ray structure of the S439T human serotonin transporter complexed with paroxetine at the central site
Structural highlights
FunctionSC6A4_HUMAN Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.[1] [2] [3] Publication Abstract from PubMedSelective 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. Structural basis for recognition of diverse antidepressants by the human serotonin transporter.,Coleman JA, Gouaux E Nat Struct Mol Biol. 2018 Feb;25(2):170-175. doi: 10.1038/s41594-018-0026-8. Epub, 2018 Jan 29. PMID:29379174[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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