4XP6

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

Summary for 4XP6

• Entry DOI: 10.2210/pdb4xp6/pdb
• Related: 4XNX 4XP1 4XP4 4XP5 4XP9 4XPA 4XPB 4XPF 4XPG 4XPH 4XPT
• Related PRD ID: PRD_900001
• Descriptor: Transporter, CHOLESTEROL HEMISUCCINATE, Antibody fragment heavy chain-protein, 9D5-heavy chain, ... (11 entities in total)
• Functional Keywords: integral membrane protein, all-alpha helical antidepressant complex, tranport protein-inhibitor complex, tranport protein/inhibitor
• Biological source: Drosophila melanogaster (Fruit fly); More
• Total number of polymer chains: 3
• Total formula weight: 108356.74

Authors

Aravind, P.,Wang, K.,Gouaux, E. (deposition date: 2015-01-16, release date: 2015-05-13, Last modification date: 2024-10-09)

Primary citation

Wang, K.H.,Penmatsa, A.,Gouaux, E.
Neurotransmitter and psychostimulant recognition by the dopamine transporter.
Nature, 521:322-327, 2015

PubMed 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.

PubMed: 25970245
DOI: 10.1038/nature14431

Experimental method

X-RAY DIFFRACTION (3.1 Å)