6awp

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X-ray structure of the ts3 human serotonin transporter complexed with fluvoxamine at the central site

Structural highlights

6awp is a 3 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.8Å
Ligands:CL, CLR, FVX, NA, NAG
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SC6A4_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 PubMed

Selective 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.

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Citations
18 reviews cite this structure
Monoamine transporters: structure, intrinsic dynamics and allosteric regulation.
Cheng et al. (2019)
17 more
50 other articles
No citations found

See Also

References

  1. ↑ Brenner B, Harney JT, Ahmed BA, Jeffus BC, Unal R, Mehta JL, Kilic F. Plasma serotonin levels and the platelet serotonin transporter. J Neurochem. 2007 Jul;102(1):206-15. Epub 2007 May 15. PMID:17506858 doi:http://dx.doi.org/10.1111/j.1471-4159.2007.04542.x
  2. ↑ Ahmed BA, Jeffus BC, Bukhari SI, Harney JT, Unal R, Lupashin VV, van der Sluijs P, Kilic F. Serotonin transamidates Rab4 and facilitates its binding to the C terminus of serotonin transporter. J Biol Chem. 2008 Apr 4;283(14):9388-98. doi: 10.1074/jbc.M706367200. Epub 2008, Jan 28. PMID:18227069 doi:http://dx.doi.org/10.1074/jbc.M706367200
  3. ↑ Ahmed BA, Bukhari IA, Jeffus BC, Harney JT, Thyparambil S, Ziu E, Fraer M, Rusch NJ, Zimniak P, Lupashin V, Tang D, Kilic F. The cellular distribution of serotonin transporter is impeded on serotonin-altered vimentin network. PLoS One. 2009;4(3):e4730. doi: 10.1371/journal.pone.0004730. Epub 2009 Mar 9. PMID:19270731 doi:http://dx.doi.org/10.1371/journal.pone.0004730
  4. ↑ Coleman JA, Gouaux E. Structural basis for recognition of diverse antidepressants by the human serotonin transporter. Nat Struct Mol Biol. 2018 Feb;25(2):170-175. doi: 10.1038/s41594-018-0026-8. Epub, 2018 Jan 29. PMID:29379174 doi:http://dx.doi.org/10.1038/s41594-018-0026-8

Contents


PDB ID 6awp

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