Crystal structures of Entamoeba histolytica lysyl-tRNA synthetase reveal conformational changes upon lysine binding and a specific helix bundle domain

• EhKRS structures give snapshots of the lysine-adenylate formation.
• The active site is highly conserved and closes around the bound lysyl-adenylate.
• The EELP domain is not visible in the crystal structures.
• An Entamoeba-specific insertion fold into a small helix bundle.
• The helix bundle may contact the bound tRNA molecule.

The class II lysyl-tRNA synthetases (KRS) are conserved aminoacyl-tRNA synthetases that attach lysine to the cognate tRNA in a two-step mechanism. The enzyme from the parasitic protozoan Entamoeba histolytica was crystallized in the presence of small ligands to generate snapshots of the lysine-adenylate formation. The residues involved in lysine activation are highly conserved and the active site closes around the lysyl-adenylate, as observed in bacterial KRS. The Entamoeba EMAPII-like polypeptide is not resolved in the crystals, but another Entamoeba-specific insertion could be modeled as a small helix bundle that may contribute to tRNA binding through interaction with the tRNA hinge.