Aminoacyl-tRNA synthetases are very specific for aminoacylation of tRNAs with the correct cognate amino acids. However, there is a possibility of a mismatch between the tRNA and its cognate amino acid. This error is corrected by the inherent proof-reading activity of the aminoacyl-tRNA synthetase. In case of two very similar amino acids, namely valine and isoleucine, isoleucyl-tRNA synthetase employs the following possible approaches for an error-free aminoacylation.

P. It removes an incorrect amino acid by hydrolyzing the aminoacyl-AMP linkage following the first reaction step.

Q. It is activated for proof-reading activity, leading to breakage of the bond between the wrong amino acid and tRNA.

R. It has an intrinsic ability to recognize the structural difference between amino acids leading to abortive elimination of the non-cognate amino acid.

S. It gets sequestered in the second step with the wrong amino acid, and that freezes the aminoacylation process.

Which of the following combinations is correct?