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| | <StructureSection load='4xpf' size='340' side='right'caption='[[4xpf]], [[Resolution|resolution]] 3.27Å' scene=''> | | <StructureSection load='4xpf' size='340' side='right'caption='[[4xpf]], [[Resolution|resolution]] 3.27Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4xpf]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Drome Drome] 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=4XPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XPF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4xpf]] 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=4XPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XPF FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=42F:METHYL+(1R,2S,3S,5S)-3-(4-IODOPHENYL)-8-METHYL-8-AZABICYCLO[3.2.1]OCTANE-2-CARBOXYLATE'>42F</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=DMU:DECYL-BETA-D-MALTOPYRANOSIDE'>DMU</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=P4G:1-ETHOXY-2-(2-ETHOXYETHOXY)ETHANE'>P4G</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.273Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xnu|4xnu]], [[4xnx|4xnx]], [[4xp1|4xp1]], [[4xp4|4xp4]], [[4xp5|4xp5]], [[4xp6|4xp6]], [[4xp9|4xp9]], [[4xpa|4xpa]], [[4xpb|4xpb]], [[4xpg|4xpg]], [[4xph|4xph]], [[4xpt|4xpt]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=42F:METHYL+(1R,2S,3S,5S)-3-(4-IODOPHENYL)-8-METHYL-8-AZABICYCLO[3.2.1]OCTANE-2-CARBOXYLATE'>42F</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=DMU:DECYL-BETA-D-MALTOPYRANOSIDE'>DMU</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=P4G:1-ETHOXY-2-(2-ETHOXYETHOXY)ETHANE'>P4G</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dDAT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 DROME])</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=4xpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xpf OCA], [https://pdbe.org/4xpf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xpf RCSB], [https://www.ebi.ac.uk/pdbsum/4xpf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xpf 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=4xpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xpf OCA], [http://pdbe.org/4xpf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xpf RCSB], [http://www.ebi.ac.uk/pdbsum/4xpf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xpf 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: Drome]] | + | [[Category: Drosophila melanogaster]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Gouaux, E]] | + | [[Category: Gouaux E]] |
| - | [[Category: Penmatsa, A]] | + | [[Category: Penmatsa A]] |
| - | [[Category: Wang, K H]] | + | [[Category: Wang KH]] |
| - | [[Category: All alpha-helical integral membrane protein]]
| + | |
| - | [[Category: Transport protein-inhibitor complex]]
| + | |
| Structural highlights
4xpf 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.
| | Method: | X-ray diffraction, Resolution 3.273Å |
| 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
Na(+)/Cl(-)-coupled biogenic amine transporters are the primary targets of therapeutic and abused drugs, ranging from antidepressants to the psychostimulants cocaine and amphetamines, and to their cognate substrates. Here we determine X-ray crystal structures of the Drosophila melanogaster dopamine transporter (dDAT) bound to its substrate dopamine, a substrate analogue 3,4-dichlorophenethylamine, the psychostimulants d-amphetamine and methamphetamine, or to cocaine and cocaine analogues. All ligands bind to the central binding site, located approximately halfway across the membrane bilayer, in close proximity to bound sodium and chloride ions. The central binding site recognizes three chemically distinct classes of ligands via conformational changes that accommodate varying sizes and shapes, thus illustrating molecular principles that distinguish substrates from inhibitors in biogenic amine transporters.
Neurotransmitter and psychostimulant recognition by the dopamine transporter.,Wang KH, Penmatsa A, Gouaux E Nature. 2015 May 21;521(7552):322-7. doi: 10.1038/nature14431. Epub 2015 May 11. PMID:25970245[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
- ↑ 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
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