PDBsum entry 4xph

Protein transport/inhibitor

PDB id: 4xph

Contents

Protein chains

534 a.a.

214 a.a.

219 a.a.

Ligands

BGC-GLC

P4G

42J

CLR ×2

Metals

_NA ×3

_CL

Waters ×15

PDB id:

4xph

Name:

Protein transport/inhibitor

Title:

X-ray structure of drosophila dopamine transporter with subsiteb mutations (d121g/s426m) bound to 3,4dichlorophenethylamine

Structure:

Transporter. Chain: a. Engineered: yes. Mutation: yes. Antibody fragment light chain. Chain: l. Engineered: yes. Antibody fragment heavy chain. Chain: h.

Source:

Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Gene: dat, cg8380. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293s. Mus musculus. Organism_taxid: 10090.

Resolution:

2.90Å R-factor: 0.242 R-free: 0.277

Authors:

A.Penmatsa,K.Wang,E.Gouaux

Key ref:

K.H.Wang et al. (2015). Neurotransmitter and psychostimulant recognition by the dopamine transporter. Nature, 521, 322-327. PubMed id: 25970245 DOI: 10.1038/nature14431

Date:

17-Jan-15 Release date: 06-May-15

Protein chain

Q7K4Y6  (DAT_DROME) -  Sodium-dependent dopamine transporter from Drosophila melanogaster

Seq: 631 a.a.

Struc: 534 a.a.*

Protein chain

No UniProt id for this chain

Struc: 214 a.a.

Protein chain

No UniProt id for this chain

Struc: 219 a.a.

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

DOI no: 10.1038/nature14431

Nature 521:322-327 (2015)

PubMed id: 25970245

Neurotransmitter and psychostimulant recognition by the dopamine transporter.

K.H.Wang, A.Penmatsa, E.Gouaux.

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.