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.
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| Method: | X-ray diffraction, Resolution 3Å |
| Ligands: | 41X, BGC, CL, CLR, GLC, NA, PRD_900018 |
| 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:https://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:https://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:https://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:https://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:https://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:https://dx.doi.org/10.1038/nsmb.3029
