Structural Overview
The major structural elements of ValRS, like other class-Ia aminoacyl-tRNA synthetases, are a helical insertion into the N-terminal half of a Rossmann fold domain and an α-helix bundle domain near the C-terminus[3]. Additionally, ValRS has a large editing domain important in the discrimination between valine and structurally similar amino acids. A positively charged (SC-fold) domain contacts the D-loop of tRNA(val), creating a space between the anticodon recognition and editing domains where the tRNA is "pinched" and held onto. This positive patch lines up with the negative backbone of the D-stem, with the Arg570 side chain contacting the oxygens of C11 and C25, the aromatic nitrogen of Trp571 forming weak bonds with the oxygens of U12, and the side chain of Arg566 hydrogen bonding with the backbone of C13.
tRNA(val) Recognition
The anticodon of tRNA(val) is recognized and bound by a highly conserved α-helix bundle domain near the C-terminus. Upon binding to ValRS, the anitcodon loop of tRNA(val) becomes extensively unwound and deformed, leading to disordered anticodon. In this state, the first base of the anticodon (C34) is wound out towards the solvent and does not form any interactions with ValRS (which is likely important in wobble during translation). Instead, A35 and C36 become the primary identity elements of the tRNA(val) anticodon. A35 and C36 are spatially stabilized through stacking interactions which may be important in tRNA discrimination as both the A34-C35 and A36-C37 sequences are quite rare in natural tRNA species[4].
Amino Acid Discrimination
