View source for 6awq


==Anomalous chloride signal reveals the position of sertraline complexed with the serotonin transporter at the central site==
<StructureSection load='6awq' size='340' side='right'caption='[[6awq]], [[Resolution|resolution]] 4.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6awq]] 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=6AWQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AWQ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 4.046&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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>, <scene name='pdbligand=SRE:(1S,4S)-4-(3,4-DICHLOROPHENYL)-N-METHYL-1,2,3,4-TETRAHYDRONAPHTHALEN-1-AMINE'>SRE</scene></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=6awq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6awq OCA], [https://pdbe.org/6awq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6awq RCSB], [https://www.ebi.ac.uk/pdbsum/6awq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6awq ProSAT]</span></td></tr>
</table>
== Function ==
[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;">
== 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<ref>PMID:29379174</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6awq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[Serotonin Transporter|Serotonin Transporter]]
*[[3D structures of non-human antibody|3D structures of non-human antibody]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Coleman JA]]
[[Category: Gouaux E]]