L-lysine 6-aminotransferase (LAT) (LAT)

L-lysine 6-aminotransferase (LAT) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that plays a critical role in the catabolism of L-lysine (UniProt P9WNX3; BRENDA EC 2.6.1.36). In pathogens such as Mycobacterium tuberculosis, LAT catalyzes the first step of the pipecolic acid pathway, converting L-lysine into L-delta-1-piperideine-6-carboxylate (PubMed 21663355). This metabolic route is particularly significant during the latent phase of tuberculosis, as it contributes to the pathogen's ability to persist within the host under stressful conditions (PubMed 16430314). Because humans primarily utilize the saccharopine pathway for lysine degradation rather than the LAT-mediated pathway, this enzyme represents a promising target for selective antibacterial therapy (PubMed 21663355). Research into LAT inhibitors focuses on small molecules that can bind to the active site and block the transamination reaction (PubMed 16430314). However, a major challenge in drug development is ensuring selectivity over human aminotransferases, specifically ornithine aminotransferase, which shares structural similarities with LAT (PubMed 21663355). Successful inhibition of LAT could lead to new treatments for multi-drug resistant tuberculosis by targeting the metabolic flexibility of the bacterium.

Other names

L-lysine-epsilon-aminotransferaseLysine 6-aminotransferaseLysine epsilon-aminotransferaseLysATLysine 6-transaminase

Competitive inhibition of the pyridoxal 5'-phosphate-dependent transamination reaction