4xnx

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==X-ray structure of Drosophila dopamine transporter in complex with reboxetine==
==X-ray structure of Drosophila dopamine transporter in complex with reboxetine==
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<StructureSection load='4xnx' size='340' side='right' caption='[[4xnx]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
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<StructureSection load='4xnx' size='340' side='right'caption='[[4xnx]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4xnx]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XNX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XNX FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4xnx]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster] 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=4XNX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XNX FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=41X:(2R)-2-[(R)-(2-ETHOXYPHENOXY)(PHENYL)METHYL]MORPHOLINE'>41X</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=N9S:4-O-ALPHA-D-GLUCOPYRANOSYL-BETA-D-GLUCOPYRANOSE'>N9S</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4m48|4m48]], [[4xp1|4xp1]], [[4xp4|4xp4]], [[4xp5|4xp5]], [[4xp6|4xp6]], [[4xp9|4xp9]], [[4xpa|4xpa]], [[4xpb|4xpb]], [[4xpf|4xpf]], [[4xpg|4xpg]], [[4xph|4xph]], [[4xpt|4xpt]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=41X:(2R)-2-[(R)-(2-ETHOXYPHENOXY)(PHENYL)METHYL]MORPHOLINE'>41X</scene>, <scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PRD_900018:beta-maltose'>PRD_900018</scene></td></tr>
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<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=4xnx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xnx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4xnx RCSB], [http://www.ebi.ac.uk/pdbsum/4xnx PDBsum]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4xnx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xnx OCA], [https://pdbe.org/4xnx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xnx RCSB], [https://www.ebi.ac.uk/pdbsum/4xnx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xnx ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Most antidepressants elicit their therapeutic benefits through selective blockade of Na+/Cl--coupled neurotransmitter transporters. Here we report X-ray structures of the Drosophila melanogaster dopamine transporter in complexes with the polycyclic antidepressants nisoxetine or reboxetine. The inhibitors stabilize the transporter in an outward-open conformation by occupying the substrate-binding site. These structures explain how interactions between the binding pocket and substituents on the aromatic rings of antidepressants modulate drug-transporter selectivity.
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X-ray structures of Drosophila dopamine transporter in complex with nisoxetine and reboxetine.,Penmatsa A, Wang KH, Gouaux E Nat Struct Mol Biol. 2015 May 11. doi: 10.1038/nsmb.3029. PMID:25961798<ref>PMID:25961798</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4xnx" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Antibody 3D structures|Antibody 3D structures]]
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*[[3D structures of non-human antibody|3D structures of non-human antibody]]
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Aravind, P]]
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[[Category: Drosophila melanogaster]]
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[[Category: Gouaux, E]]
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[[Category: Large Structures]]
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[[Category: Wang, K]]
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[[Category: Mus musculus]]
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[[Category: All-alpha helical antidepressant complex]]
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[[Category: Aravind P]]
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[[Category: Integral membrane protein]]
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[[Category: Gouaux E]]
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[[Category: Transport protein-inhibitor complex]]
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[[Category: Wang K]]

Current revision

X-ray structure of Drosophila dopamine transporter in complex with reboxetine

PDB ID 4xnx

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