PDBsum entry 4xnx

Transport protein/inhibitor

PDB id: 4xnx

Contents

Protein chains

536 a.a.

214 a.a.

216 a.a.

Ligands

BGC-GLC

CLR ×2

41X

Metals

_NA ×2

_CL

Waters ×6

PDB id:

4xnx

Name:

Transport protein/inhibitor

Title:

X-ray structure of drosophila dopamine transporter in complex with reboxetine

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, dmel_cg8380. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: gnti-hek293s. Mus musculus. Organism_taxid: 10090.

Resolution:

3.00Å R-factor: 0.219 R-free: 0.258

Authors:

P.Aravind,K.Wang,E.Gouaux

Key ref:

A.Penmatsa et al. (2015). X-ray structures of Drosophila dopamine transporter in complex with nisoxetine and reboxetine. Nat Struct Biol, 22, 506-508. PubMed id: 25961798 DOI: 10.1038/nsmb.3029

Date:

16-Jan-15 Release date: 13-May-15

Protein chain

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

Seq: 631 a.a.

Struc: 536 a.a.*

Protein chain

No UniProt id for this chain

Struc: 214 a.a.

Protein chain

No UniProt id for this chain

Struc: 216 a.a.

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1038/nsmb.3029

Nat Struct Biol 22:506-508 (2015)

PubMed id: 25961798

X-ray structures of Drosophila dopamine transporter in complex with nisoxetine and reboxetine.

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

ABSTRACT

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.