Bacterial Leucine Transporter (LeuT)

The Bacterial Leucine Transporter (LeuT) is a sodium-dependent symporter from the thermophilic bacterium Aquifex aeolicus and a member of the Neurotransmitter:Sodium Symporter (NSS) family [1, 2]. It functions by coupling the inward movement of sodium ions to the transport of small hydrophobic amino acids, such as leucine and alanine, across the cell membrane [2, 4]. LeuT serves as the primary structural and mechanistic model for the human Solute Carrier 6 (SLC6) family, which includes the serotonin (SERT), dopamine (DAT), and norepinephrine (NET) transporters [1, 3, 8]. These human transporters are major therapeutic targets for the treatment of psychiatric and neurological conditions, including major depressive disorder, ADHD, and anxiety [1, 8]. LeuT has been instrumental in structural biology, providing the first high-resolution insights into the alternating access mechanism and the binding modes of various antidepressants [3, 6, 7]. It interacts with several classes of drugs, including tricyclic antidepressants (TCAs) like clomipramine and selective serotonin reuptake inhibitors (SSRIs), which often act as non-competitive inhibitors by binding to an extracellular vestibule site [3, 4]. By studying LeuT, researchers have gained a fundamental understanding of how therapeutic agents and drugs of abuse, such as cocaine, modulate neurotransmitter reuptake in the central nervous system [1, 4].

Other names

LeuTAaSodium-dependent leucine transporterNSS homologAquifex aeolicus leucine transporter

Inhibition of substrate transport by stabilizing specific conformational states (e.g., outward-facing or occluded) through binding at the S1 or S2 sites.