6vrk: Difference between revisions
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<StructureSection load='6vrk' size='340' side='right'caption='[[6vrk]], [[Resolution|resolution]] 4.10Å' scene=''> | <StructureSection load='6vrk' size='340' side='right'caption='[[6vrk]], [[Resolution|resolution]] 4.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6vrk]] is a 3 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6vrk]] 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=6VRK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VRK FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=RFS: | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.1Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=RFS:(3~{S},4~{R})-3-(1,3-benzodioxol-5-yloxymethyl)-4-(4-bromophenyl)piperidine'>RFS</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6vrk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vrk OCA], [https://pdbe.org/6vrk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vrk RCSB], [https://www.ebi.ac.uk/pdbsum/6vrk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vrk ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 22: | Line 20: | ||
==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 == | ||
| Line 27: | Line 26: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mus musculus]] | ||
[[Category: Coleman | [[Category: Coleman JA]] | ||
[[Category: Navratna | [[Category: Navratna V]] | ||
[[Category: Yang | [[Category: Yang D]] | ||
Latest revision as of 11:25, 17 October 2024
Cryo-EM structure of the wild-type human serotonin transporter complexed with Br-paroxetine and 8B6 FabCryo-EM structure of the wild-type human serotonin transporter complexed with Br-paroxetine and 8B6 Fab
Structural highlights
Publication Abstract from PubMedAntidepressants 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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