Computational and Experimental Studies to Unravel the Role of Editing Domain of Bacterial Prolyl-tRNA Synthetases in Amino Acid Activation

Abstract

Prolyl-tRNA synthetases (ProRSs) are multi-domain proteins that catalyze covalent attachment of proline to the 3'-end of the tRNA[superscript]Pro. ProRSs from all three kingdoms of life are known to misactivate alanine and form mischarged tRNA[superscript]Pro. To maintain high fidelity in protein synthesis, some ProRSs have acquired editing mechanisms. The insertion domain (INS, ~180 amino acids) of Escherichia coli (Ec) ProRS is the post-transfer editing active site that hydrolyzes specifically mischarged alanyl-tRNA[superscript]Pro. Experimental studies have demonstrated that the INS domain of Ec ProRS also has a significant impact on amino acid binding and activation. To explore the exact role the INS (editing domain) plays in amino acid activation, the dynamic coupling between the editing domain and various structural elements of the catalytic domain of Ec ProRS was studied by performing molecular dynamics simulations.