4xpt

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==X-ray structure of Drosophila dopamine transporter with subsiteB mutations D121G/S426M and EL2 deletion of 162-201 in complex with substrate analogue 3,4 dichlorophen ethylamine==
==X-ray structure of Drosophila dopamine transporter with subsiteB mutations D121G/S426M and EL2 deletion of 162-201 in complex with substrate analogue 3,4 dichlorophen ethylamine==
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<StructureSection load='4xpt' size='340' side='right' caption='[[4xpt]], [[Resolution|resolution]] 3.36&Aring;' scene=''>
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<StructureSection load='4xpt' size='340' side='right'caption='[[4xpt]], [[Resolution|resolution]] 3.36&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4xpt]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XPT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XPT FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4xpt]] 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=4XPT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XPT 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=42J:2-(3,4-DICHLOROPHENYL)ETHANAMINE'>42J</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>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</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]] 3.36&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4m48|4m48]], [[4xnu|4xnu]], [[4xnx|4xnx]], [[4xp1|4xp1]], [[4xp4|4xp4]], [[4xp5|4xp5]], [[4xp6|4xp6]], [[4xp9|4xp9]], [[4xpa|4xpa]], [[4xpb|4xpb]], [[4xpf|4xpf]], [[4xpg|4xpg]], [[4xph|4xph]]</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=42J:2-(3,4-DICHLOROPHENYL)ETHANAMINE'>42J</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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PRD_900018:beta-maltose'>PRD_900018</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</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=4xpt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xpt OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4xpt RCSB], [http://www.ebi.ac.uk/pdbsum/4xpt 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=4xpt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xpt OCA], [https://pdbe.org/4xpt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xpt RCSB], [https://www.ebi.ac.uk/pdbsum/4xpt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xpt 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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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.
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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<ref>PMID:25970245</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 4xpt" 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: Protein transport-inhibitor complex]]
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[[Category: Wang K]]
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[[Category: Transport protein-inhibitor complex]]
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Current revision

X-ray structure of Drosophila dopamine transporter with subsiteB mutations D121G/S426M and EL2 deletion of 162-201 in complex with substrate analogue 3,4 dichlorophen ethylamine

PDB ID 4xpt

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