Allosteric modulatory effects of SRI-20041 and SRI-30827 on cocaine and HIV-1 Tat protein binding to human dopamine transporter.

ABSTRACT: Dopamine transporter (DAT) is the target of cocaine and HIV-1 transactivator of transcription (Tat) protein. Identifying allosteric modulatory molecules with potential attenuation of cocaine and Tat binding to DAT are of great scientific and clinical interest. We demonstrated that tyrosine 470 and 88 act as functional recognition residues in human DAT (hDAT) for Tat-induced inhibition of DA transport and transporter conformational transitions. Here we investigated the allosteric modulatory effects of two allosteric ligands, SRI-20041 and SRI-30827 on cocaine binding on wild type (WT) hDAT, Y470 H and Y88 F mutants. Effect of SRI-30827 on Tat-induced inhibition of [³H]WIN35,428 binding was also determined. Compared to a competitive DAT inhibitor indatraline, both SRI-compounds

SUBMITTER: Sun WL 

PROVIDER: S-EPMC5473888 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature