TABLE 1

MIC values for compound 1-resistant mutantsa

OrganismMIC (μg/ml)b
M. tuberculosis
    H37Rv0.6–1.3
    RM1leuS Y435C21
    RM2leuS S311L21
    RM3leuS D450Y21
    RM4leuS S311L21
M. smegmatis
    ATCC 7000841
    RM1leuS Δ421–462>256
    RM2leuS A428T64
    RM3leuS R435C8
    RM4leuS A428T64
  • a Residues Y435 and D450 stabilize the adduct formed by compound 1 with AMP in the editing site of M. tuberculosis LeuRS (Fig. 4B). Residue S311, like the equivalent E. coli LeuRS residue (13), interacts with the phosphate of Ade76, thus stabilizing the adduct in the editing site. However, S311 is located at the flexible N-terminal part of our editing domain construct of M. tuberculosis LeuRS and thus is not visible in the crystal structure (Fig. 4B). RM, resistant mutant.

  • b MIC values for M. tuberculosis were determined on agar, and those for M. smegmatis were determined in liquid cultures.