Methionyl-tRNA Synthetase

Methionyl-tRNA synthetase (MetRS) is an enzyme that plays a crucial role in protein synthesis by catalyzing the attachment of the amino acid methionine to its cognate tRNA: $ \text{Met} + \text{tRNA}^\text{Met} + \text{ATP} \xrightarrow{\text{MetRS}} \text{Met-tRNA}^\text{Met} + \text{AMP} + \text{PP}_i $ MetRS is closely related to the [LeuRS-A](/class1/leu2), [LeuRS-B](/class1/leu1), [ValRS](/class1/val), and [IleRS](/class1/ile) families, which comprise subclass Ia (Gomez and Ibba, 2020). Members of subclass Ia are characterized by their hydrophobic amino acid substrates, the connecting peptide 2 (CP2) insertion, and a zinc finger (ZF, Sugiura et al. 2001), depicted below. The CP2 module is 30-40 amino acids in length (Starzyk et al. 1987) and exists as two antiparallel $\alpha$-helices on the surface of the catalytic domain. It appears to be essential for amino acid activation (Zhou et al. 2008). MetRS exists as a homodimer or a monomer, depending on the presence or absence of a C-terminal domain downstream from the [helical domain](/superfamily/class1/Anticodon_binding_domain_CRIMVL) (Crepin et al. 2004). The dimerisation domain, EMAP, is only present in certain organisms and shows an OB-fold, which is also found in paralogous RNA binding proteins (Crepin et al. 2002). In the context of MetRS, this domain improves tRNA$^\text{Met}$ binding affinity (Blanquet et al. 1973). A paralog of EMAP is also found in some forms of [TyrRS](/class1/tyr) and [PheRS](/class2/phe2) (Wolf et al. 1999), and is the [anticodon binding domain](/superfamily/class2/Anticodon_binding_domain_DNK) of subclass IIb AARS. Editing activity has been characterized in MetRS which, in contrast to other members of subclass Ia, removes mischarged amino acids at the active site as opposed to a specialized editing domain (Gomez and Ibba, 2020). This process targets non-proteinogenic amino acids, such as homocysteine, at the pre-transfer level (Jakubowski et al. 1990). MetRS is also one of several aminoacyl-tRNA synthetases expressed by mimiviruses (Abergel et al. 2007). Certain cytosolic MetRS have an N-terminal glutathione S-transferase ([GST](/superfamily/class1/GST)) domain (Hadd and Perona. 2014).

References

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