Mycobacterium tuberculosis leucyl-tRNA synthetase (LeuRS)

Mycobacterium tuberculosis leucyl-tRNA synthetase is a class I aminoacyl-tRNA synthetase enzyme responsible for linking the amino acid leucine to its cognate tRNA^Leu during translation, a process essential for bacterial protein synthesis[2][5][7]. This enzyme is required for viability and plays a key role in the growth, survival, and biofilm formation of M. tuberculosis[2][5]. Its unique structural features, particularly in the editing and tRNA-binding domains, make it an attractive therapeutic target for anti-tubercular drug development[1][4][5]. Small molecule inhibitors of LeuRS, especially those utilizing the oxaborole tRNA-trapping (OBORT) mechanism, block protein synthesis and show efficacy against drug-sensitive and drug-resistant M. tuberculosis, validating LeuRS as a promising target for next-generation antituberculosis agents[1][4][6][8].

Other names

LeuRSMtb LeuRSMtLeuRSMycobacterium tuberculosis LeuRS

Inhibition of LeuRS blocks leucylation of tRNA^Leu, halting protein synthesis in Mycobacterium tuberculosis[1][2][4] OBORT (oxaborole tRNA-trapping): covalent trapping of tRNA in the enzyme editing site, preventing protein translation[1][4][6] Direct enzymatic inhibition via small molecule binding (competitive or allosteric), including by dual-acting compounds targeting both LeuRS and other synthetases[8]