Identification of a New Allosteric Binding Site for Cocaine in Dopamine Transporter.

ABSTRACT: Dopamine (DA) transporter (DAT) is a major target for psychostimulant drugs of abuse such as cocaine that competitively binds to DAT, inhibits DA reuptake, and consequently increases synaptic DA levels. In addition to the central binding site inside DAT, the available experimental evidence suggests the existence of alternative binding sites on DAT, but detection and characterization of these sites are challenging by experiments alone. Here, we integrate multiple computational approaches to probe the potential binding sites on the wild-type Drosophila melanogaster DAT and identify a new allosteric site that displays high affinity for cocaine. This site is located on the surface of DAT, and binding of cocaine is primarily dominated by interactions with hydrophobic residues surrounding

SUBMITTER: Xu L 

PROVIDER: S-EPMC7484383 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature