FIGURE 10.

Sequence alignment showing the degeneracy of hmtLeuRS's CP1 domain in regions or sites that may be relevant to the resistance to AN2690 and the loss of tRNA-dependent pre-transfer editing in ScLeuRS and TtLeuRS. The abbreviations used are as follows: Sc(cyto), S. cerevisiae cytoplasmic LeuRS; Hs(mt), H. sapiens mitochondrial LeuRS; Tt, T. thermophilus LeuRS. Asterisks and triangles indicate residues whose mutation leads to resistance to AN2690 in ScLeuRS (T314M, L315V, R316I, T319I, C326R, C326F, G405V, N415D, and S416L) (23) and Thr²⁴⁸ in TtLeuRS, respectively. Arrows indicate certain essential residues (Lys³⁰², Tyr³³², and Arg³⁴⁶) in TtLeuRS that interact with tRNA in the post-transfer editing conformation.