View source for 6awn


==X-ray structure of the S439T human serotonin transporter complexed with paroxetine at the central site==
<StructureSection load='6awn' size='340' side='right'caption='[[6awn]], [[Resolution|resolution]] 3.62&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6awn]] 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=6AWN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AWN FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8PR:PAROXETINE'>8PR</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</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">[[5i71|5i71]], [[5i6z|5i6z]], [[5i66|5i66]], [[5i73|5i73]], [[5i74|5i74]], [[5i75|5i75]]</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]), HC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), LC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=6awn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6awn OCA], [http://pdbe.org/6awn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6awn RCSB], [http://www.ebi.ac.uk/pdbsum/6awn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6awn ProSAT]</span></td></tr>
</table>
== 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>  
<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 6awn" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[Serotonin Transporter|Serotonin Transporter]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[Category: Coleman, J A]]
[[Category: Gouaux, E]]
[[Category: Antidepressant]]
[[Category: Neurotransmitter transporter]]
[[Category: Transport protein]]