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| | <StructureSection load='4xnx' size='340' side='right'caption='[[4xnx]], [[Resolution|resolution]] 3.00Å' scene=''> | | <StructureSection load='4xnx' size='340' side='right'caption='[[4xnx]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <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> | + | <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> |
| - | </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> | + | </td></tr><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> |
| - | <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>
| + | <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> |
| - | <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://pdbe.org/4xnx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xnx RCSB], [http://www.ebi.ac.uk/pdbsum/4xnx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xnx 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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| | *[[Antibody 3D structures|Antibody 3D structures]] | | *[[Antibody 3D structures|Antibody 3D structures]] |
| | + | *[[3D structures of non-human antibody|3D structures of non-human antibody]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Drosophila melanogaster]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Aravind, P]] | + | [[Category: Mus musculus]] |
| - | [[Category: Gouaux, E]] | + | [[Category: Aravind P]] |
| - | [[Category: Wang, K]] | + | [[Category: Gouaux E]] |
| - | [[Category: All-alpha helical antidepressant complex]] | + | [[Category: Wang K]] |
| - | [[Category: Integral membrane protein]]
| + | |
| - | [[Category: Transport protein-inhibitor complex]]
| + | |
| Structural highlights
4xnx is a 3 chain structure with sequence from Drosophila melanogaster and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
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).[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
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.
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[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Porzgen P, Park SK, Hirsh J, Sonders MS, Amara SG. The antidepressant-sensitive dopamine transporter in Drosophila melanogaster: a primordial carrier for catecholamines. Mol Pharmacol. 2001 Jan;59(1):83-95. doi: 10.1124/mol.59.1.83. PMID:11125028 doi:http://dx.doi.org/10.1124/mol.59.1.83
- ↑ Wu X, Gu HH. Cocaine affinity decreased by mutations of aromatic residue phenylalanine 105 in the transmembrane domain 2 of dopamine transporter. Mol Pharmacol. 2003 Mar;63(3):653-8. doi: 10.1124/mol.63.3.653. PMID:12606774 doi:http://dx.doi.org/10.1124/mol.63.3.653
- ↑ Kume K, Kume S, Park SK, Hirsh J, Jackson FR. Dopamine is a regulator of arousal in the fruit fly. J Neurosci. 2005 Aug 10;25(32):7377-84. doi: 10.1523/JNEUROSCI.2048-05.2005. PMID:16093388 doi:http://dx.doi.org/10.1523/JNEUROSCI.2048-05.2005
- ↑ Penmatsa A, Wang KH, Gouaux E. X-ray structure of dopamine transporter elucidates antidepressant mechanism. Nature. 2013 Sep 15. doi: 10.1038/nature12533. PMID:24037379 doi:10.1038/nature12533
- ↑ Ueno T, Kume K. Functional characterization of dopamine transporter in vivo using Drosophila melanogaster behavioral assays. Front Behav Neurosci. 2014 Sep 3;8:303. doi: 10.3389/fnbeh.2014.00303., eCollection 2014. PMID:25232310 doi:http://dx.doi.org/10.3389/fnbeh.2014.00303
- ↑ Wang KH, Penmatsa A, Gouaux E. Neurotransmitter and psychostimulant recognition by the dopamine transporter. Nature. 2015 May 21;521(7552):322-7. doi: 10.1038/nature14431. Epub 2015 May 11. PMID:25970245 doi:http://dx.doi.org/10.1038/nature14431
- ↑ Penmatsa A, Wang KH, Gouaux E. X-ray structures of Drosophila dopamine transporter in complex with nisoxetine and reboxetine. Nat Struct Mol Biol. 2015 May 11. doi: 10.1038/nsmb.3029. PMID:25961798 doi:http://dx.doi.org/10.1038/nsmb.3029
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