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| | <StructureSection load='6w2c' size='340' side='right'caption='[[6w2c]], [[Resolution|resolution]] 6.30Å' scene=''> | | <StructureSection load='6w2c' size='340' side='right'caption='[[6w2c]], [[Resolution|resolution]] 6.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6w2c]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W2C OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6W2C FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6w2c]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W2C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W2C FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RFY:I-paroxetine'>RFY</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 6.3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SLC6A4, HTT, SERT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RFY:I-paroxetine'>RFY</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6w2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w2c OCA], [http://pdbe.org/6w2c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6w2c RCSB], [http://www.ebi.ac.uk/pdbsum/6w2c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6w2c ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6w2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w2c OCA], [https://pdbe.org/6w2c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w2c RCSB], [https://www.ebi.ac.uk/pdbsum/6w2c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w2c ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SC6A4_HUMAN 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.<ref>PMID:17506858</ref> <ref>PMID:18227069</ref> <ref>PMID:19270731</ref> | + | [https://www.uniprot.org/uniprot/SC6A4_HUMAN 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.<ref>PMID:17506858</ref> <ref>PMID:18227069</ref> <ref>PMID:19270731</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| | *[[Antibody 3D structures|Antibody 3D structures]] | | *[[Antibody 3D structures|Antibody 3D structures]] |
| | + | *[[Serotonin Transporter|Serotonin Transporter]] |
| | *[[3D structures of non-human antibody|3D structures of non-human antibody]] | | *[[3D structures of non-human antibody|3D structures of non-human antibody]] |
| | == References == | | == References == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Coleman, J A]] | + | [[Category: Coleman JA]] |
| - | [[Category: Navratna, V]] | + | [[Category: Navratna V]] |
| - | [[Category: Yang, D]] | + | [[Category: Yang D]] |
| - | [[Category: Antibody]]
| + | |
| - | [[Category: Antidepressant]]
| + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| - | [[Category: Transporter]]
| + | |
| Structural highlights
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
Antidepressants target the serotonin transporter (SERT) by inhibiting serotonin reuptake. Structural and biochemical studies aiming to understand binding of small-molecules to conformationally dynamic transporters like SERT often require thermostabilizing mutations and antibodies to stabilize a specific conformation, leading to questions about relationships of these structures to the bonafide conformation and inhibitor binding poses of wild-type transporter. To address these concerns, we determined the structures of N72/C13 and ts2-inactive SERT bound to paroxetine analogues using single-particle cryo-EM and x-ray crystallography, respectively. We synthesized enantiopure analogues of paroxetine containing either bromine or iodine instead of fluorine. We exploited the anomalous scattering of bromine and iodine to define the pose of these inhibitors and investigated inhibitor binding to Asn177 mutants of ts2-active SERT. These studies provide mutually consistent insights into how paroxetine and its analogues bind to the central substrate-binding site of SERT, stabilize the outward-open conformation, and inhibit serotonin transport.
Chemical and structural investigation of the paroxetine-human serotonin transporter complex.,Coleman JA, Navratna V, Antermite D, Yang D, Bull JA, Gouaux E Elife. 2020 Jul 3;9. pii: 56427. doi: 10.7554/eLife.56427. PMID:32618269[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Coleman JA, Navratna V, Antermite D, Yang D, Bull JA, Gouaux E. Chemical and structural investigation of the paroxetine-human serotonin transporter complex. Elife. 2020 Jul 3;9. pii: 56427. doi: 10.7554/eLife.56427. PMID:32618269 doi:http://dx.doi.org/10.7554/eLife.56427
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