4XP6: X-ray structure of Drosophila dopamine transporter bound to psychostimulant methamphetamine

Citation:
Abstract
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.
PDB ID: 4XP6Download
MMDB ID: 129272
PDB Deposition Date: 2015/1/16
Updated in MMDB: 2017/12
Experimental Method:
x-ray diffraction
Resolution: 3.1  Å
Source Organism:
Mus musculus
Similar Structures:
Biological Unit for 4XP6: trimeric; determined by author
Molecular Components in 4XP6
Label Count Molecule
Proteins (3 molecules)
1
Transporter
Molecule annotation
1
Antibody Fragment Heavy Chain-protein, 9d5-heavy Chain
Molecule annotation
1
Antibody Fragment Light Chain-protein, 9d5-light Chain
Molecule annotation
Chemicals (8 molecules)
1
1
2
1
3
2
4
1
5
1
6
1
7
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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