Tyrosyl tRNA synthetase mechanism

The technique of site-directed mutagenesis has been successful in providing details of the mechanism of catalysis by tyrosyl tRNA synthetase. Quantita-... 

Leatherbarrow, R.J., Fersht, A.R. and Winter, G. (1985). Transition-state stabilization in the mechanism of tyrosyl-tRNA synthetase revealed by protein engineering. Proc. Natl. Acad. Sci. USA 82, 7840-7844... 

Hydrogen-bonding interactions between the substrate and enzyme have been explored in depth in the catalytic mechanism of tyrosyl-tRNA synthetase (tyro-sine-tRNA ligase). The enzyme-catalyzed reaction occurs in two steps ... 

Figure 9 shows the theoretical transition state built into the active site of tyrosyl-tRNA synthetase, inferred from the crystal structure of the E-Tyr-AMP complex. Inspection of the active site reveals that there are no residues in position to participate in acid-base catalysis, so the crystal structure provided no obvious clues as to the reaction mechanism. However, analysis of the free energy... 

In addition to their critical role in protein synthesis, it has become clear that AARSs are involved in several other cellular pathways. Some AARSs regulate their own transcription and translation, while others contribute to splicing activities in mitochondria. Nuclear aminoacylation of tRNAs by imported AARSs is thought to be a quality control mechanism to ensure that only mature, fully active tRNAs are released efficiently to the cytoplasm for protein synthesis. Programmed cell death (apoptosis) also appears to have an AARS component—human tyrosyl-tRNA synthetase can be proteolytically cleaved into two polypeptides with distinct cytokine activities, despite the lack of such activity in the full-length TyrRS. It is likely that in time many more nontranslational functions of AARS will be identified. 

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