7wgd
From Proteopedia
(Difference between revisions)
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| - | == | + | ==X-ray structure of thermostabilized Drosophila dopamine transporter with GABA transporter1-like substitutions in the binding site, in substrate-free form.== |
| - | <StructureSection load='7wgd' size='340' side='right'caption='[[7wgd]]' scene=''> | + | <StructureSection load='7wgd' size='340' side='right'caption='[[7wgd]], [[Resolution|resolution]] 3.20Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WGD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WGD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7wgd]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WGD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WGD FirstGlance]. <br> |
| - | </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=7wgd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wgd OCA], [https://pdbe.org/7wgd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wgd RCSB], [https://www.ebi.ac.uk/pdbsum/7wgd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wgd ProSAT]</span></td></tr> | + | </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=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</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=7wgd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wgd OCA], [https://pdbe.org/7wgd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wgd RCSB], [https://www.ebi.ac.uk/pdbsum/7wgd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wgd ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/DAT_DROME DAT_DROME]] Sodium-dependent dopamine transporter which terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals (PubMed:11125028, PubMed:12606774, PubMed:24037379, PubMed:25970245). Also transports tyramine and norepinephrine, shows less efficient transport of octopamine and does not transport serotonin (PubMed:11125028, PubMed:12606774). Plays a role in the regulation of the rest/activity cycle (PubMed:16093388, PubMed:25232310).<ref>PMID:11125028</ref> <ref>PMID:12606774</ref> <ref>PMID:16093388</ref> <ref>PMID:24037379</ref> <ref>PMID:25232310</ref> <ref>PMID:25970245</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter, and its levels in the synaptic space are controlled by the GABA transporter isoforms (GATs). GATs are structurally related to biogenic amine transporters but display interactions with distinct inhibitors used as anti-epileptics. In this study, we engineer the binding pocket of Drosophila melanogaster dopamine transporter to resemble GAT1 and determine high-resolution X-ray structures of the modified transporter in the substrate-free state and in complex with GAT1 inhibitors NO711 and SKF89976a that are analogs of tiagabine, a medication prescribed for the treatment of partial seizures. We observe that the primary binding site undergoes substantial shifts in subsite architecture in the modified transporter to accommodate the two GAT1 inhibitors. We also observe that SKF89976a additionally interacts at an allosteric site in the extracellular vestibule, yielding an occluded conformation. Interchanging SKF89976a interacting residue in the extracellular loop 4 between GAT1 and dDAT suggests a role for this motif in the selective control of neurotransmitter uptake. Our findings, therefore, provide vital insights into the organizational principles dictating GAT1 activity and inhibition. | ||
| + | |||
| + | Structural insights into GABA transport inhibition using an engineered neurotransmitter transporter.,Joseph D, Nayak SR, Penmatsa A EMBO J. 2022 Jul 7:e110735. doi: 10.15252/embj.2022110735. PMID:35796008<ref>PMID:35796008</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7wgd" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Joseph, D]] |
| + | [[Category: Penmatsa, A]] | ||
| + | [[Category: Antibody fragment]] | ||
| + | [[Category: Gaba transporter]] | ||
| + | [[Category: Membrane protein]] | ||
| + | [[Category: Neurotransmitter transporter]] | ||
Revision as of 07:18, 20 July 2022
X-ray structure of thermostabilized Drosophila dopamine transporter with GABA transporter1-like substitutions in the binding site, in substrate-free form.
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