Molecular basis for the dopamine reuptake and inhibition mechanism of human dopamine transporter - PubMed
3 hours ago
- #antidepressant inhibition
- #neurotransmitter reuptake
- #dopamine transporter
- The study reveals the molecular mechanisms of dopamine (DA) reuptake and inhibition by the human dopamine transporter (hDAT).
- It presents structures of full-length hDAT in apo state and in complexes with substrates and antidepressants like bupropion and vanoxerine.
- Antidepressants bind at the central site of hDAT to inhibit substrate transport, offering a structural basis for therapeutic agent design.
- Potassium ions may regulate hDAT conformational transitions, as suggested by structural analysis, functional assays, and molecular dynamics simulations.
- hDAT dysfunction is linked to neurological disorders such as Parkinson's, depression, and schizophrenia, highlighting the importance of these findings.