6dzz: Difference between revisions

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 <StructureSection load='6dzz' size='340' side='right'caption='[[6dzz]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6dzz]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DZZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DZZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6dzz]] 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=6DZZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DZZ FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HJM:(5beta)-12-methoxyibogamine'>HJM</scene>, <scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=6dzz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dzz OCA], [http://pdbe.org/6dzz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dzz RCSB], [http://www.ebi.ac.uk/pdbsum/6dzz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dzz 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 ==
+The serotonin transporter (SERT) regulates neurotransmitter homeostasis through the sodium- and chloride-dependent recycling of serotonin into presynaptic neurons(1-3). Major depression and anxiety disorders are treated using selective serotonin reuptake inhibitors-small molecules that competitively block substrate binding and thereby prolong neurotransmitter action(2,4). The dopamine and noradrenaline transporters, together with SERT, are members of the neurotransmitter sodium symporter (NSS) family. The transport activities of NSSs can be inhibited or modulated by cocaine and amphetamines(2,3), and genetic variants of NSSs are associated with several neuropsychiatric disorders including attention deficit hyperactivity disorder, autism and bipolar disorder(2,5). Studies of bacterial NSS homologues-including LeuT-have shown how their transmembrane helices (TMs) undergo conformational changes during the transport cycle, exposing a central binding site to either side of the membrane(1,6-12). However, the conformational changes associated with transport in NSSs remain unknown. To elucidate structure-based mechanisms for transport in SERT we investigated its complexes with ibogaine, a hallucinogenic natural product with psychoactive and anti-addictive properties(13,14). Notably, ibogaine is a non-competitive inhibitor of transport but displays competitive binding towards selective serotonin reuptake inhibitors(15,16). Here we report cryo-electron microscopy structures of SERT-ibogaine complexes captured in outward-open, occluded and inward-open conformations. Ibogaine binds to the central binding site, and closure of the extracellular gate largely involves movements of TMs 1b and 6a. Opening of the intracellular gate involves a hinge-like movement of TM1a and the partial unwinding of TM5, which together create a permeation pathway that enables substrate and ion diffusion to the cytoplasm. These structures define the structural rearrangements that occur from the outward-open to inward-open conformations, and provide insight into the mechanism of neurotransmitter transport and ibogaine inhibition.
+Serotonin transporter-ibogaine complexes illuminate mechanisms of inhibition and transport.,Coleman JA, Yang D, Zhao Z, Wen PC, Yoshioka C, Tajkhorshid E, Gouaux E Nature. 2019 May;569(7754):141-145. doi: 10.1038/s41586-019-1135-1. Epub 2019 Apr, 24. PMID:31019304<ref>PMID:31019304</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6dzz" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Coleman, J A]]
 [[Category: Gouaux, E]]