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5i75

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Revision as of 13:35, 16 November 2017

X-ray structure of the ts3 human serotonin transporter complexed with s-citalopram at the central site and Br-citalopram at the allosteric site

Structural highlights

5i75 is a 3 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , ,
Related:	5i74, 5i73, 5i71, 5i6z, 5i6x, 5i66
Gene:	SLC6A4, HTT, SERT (HUMAN)
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

The serotonin transporter (SERT) terminates serotonergic signalling through the sodium- and chloride-dependent reuptake of neurotransmitter into presynaptic neurons. SERT is a target for antidepressant and psychostimulant drugs, which block reuptake and prolong neurotransmitter signalling. Here we report X-ray crystallographic structures of human SERT at 3.15 A resolution bound to the antidepressants (S)-citalopram or paroxetine. Antidepressants lock SERT in an outward-open conformation by lodging in the central binding site, located between transmembrane helices 1, 3, 6, 8 and 10, directly blocking serotonin binding. We further identify the location of an allosteric site in the complex as residing at the periphery of the extracellular vestibule, interposed between extracellular loops 4 and 6 and transmembrane helices 1, 6, 10 and 11. Occupancy of the allosteric site sterically hinders ligand unbinding from the central site, providing an explanation for the action of (S)-citalopram as an allosteric ligand. These structures define the mechanism of antidepressant action in SERT, and provide blueprints for future drug design.

X-ray structures and mechanism of the human serotonin transporter.,Coleman JA, Green EM, Gouaux E Nature. 2016 Apr 21;532(7599):334-9. doi: 10.1038/nature17629. Epub 2016 Apr 6. PMID:27049939^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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, Green EM, Gouaux E. X-ray structures and mechanism of the human serotonin transporter. Nature. 2016 Apr 21;532(7599):334-9. doi: 10.1038/nature17629. Epub 2016 Apr 6. PMID:27049939 doi:http://dx.doi.org/10.1038/nature17629

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5i75"

@@ Line 3: / Line 3: @@
 <StructureSection load='5i75' size='340' side='right' caption='[[5i75]], [[Resolution|resolution]] 3.49&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5i75]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I75 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5I75 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5i75]] 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=5I75 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5I75 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=68P:(1S)-1-[3-(DIMETHYLAMINO)PROPYL]-1-(4-FLUOROPHENYL)-1,3-DIHYDRO-2-BENZOFURAN-5-CARBONITRILE'>68P</scene>, <scene name='pdbligand=69D:(1S)-1-(4-BROMOPHENYL)-1-[3-(DIMETHYLAMINO)PROPYL]-1,3-DIHYDRO-2-BENZOFURAN-5-CARBONITRILE'>69D</scene>, <scene name='pdbligand=C14:TETRADECANE'>C14</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5i74|5i74]], [[5i73|5i73]], [[5i71|5i71]], [[5i6z|5i6z]], [[5i6x|5i6x]], [[5i66|5i66]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5i75 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i75 OCA], [http://pdbe.org/5i75 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i75 RCSB], [http://www.ebi.ac.uk/pdbsum/5i75 PDBsum]</span></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5i75 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i75 OCA], [http://pdbe.org/5i75 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i75 RCSB], [http://www.ebi.ac.uk/pdbsum/5i75 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i75 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 </div>
 <div class="pdbe-citations 5i75" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[3D structures of antibody|3D structures of antibody]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Coleman, J A]]
 [[Category: Gouaux, E]]
 [[Category: Green, E M]]
 [[Category: Membrane protein]]

5i75

From Proteopedia

Revision as of 13:35, 16 November 2017

X-ray structure of the ts3 human serotonin transporter complexed with s-citalopram at the central site and Br-citalopram at the allosteric site

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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