MetRS

MetRS, or methionyl-tRNA synthetase, is an enzyme that catalyzes the aminoacylation of tRNA^Met with methionine, the first amino acid incorporated into protein chains in bacteria and many organisms. It belongs to class I aminoacyl-tRNA synthetases and typically forms a homodimer. The enzyme recognizes methionine and the tRNA^Met isoacceptor(s) and catalyzes two reactions: activation of methionine with ATP to form Met-AMP, followed by transfer of Met to the 3'-end of tRNA^Met, producing Met-tRNA^Met.

During bacterial translation initiation, the cellular formyltransferase then adds a formyl group to the Met on initiator tRNA^fMet, producing fMet-tRNA^fMet, which is used to start protein synthesis. In archaea and eukaryotes, no formylation step is performed; MetRS charges tRNA^Met that participates in elongation.

Structural features include a catalytic Rossmann-like domain containing the characteristic HIGH and KMSKS sequence motifs typical of class I aaRS, and an anticodon- or tRNA-binding domain. Some bacterial MetRS enzymes possess an editing domain (INS) that hydrolyzes mischarged amino acids to maintain accuracy, preventing incorporation of analogs such as homoserine or norleucine.

MetRS is essential for translation and cell viability in most organisms. The enzyme is encoded by metS in bacteria (with variations such as metRS in some species) and has mitochondrial and cytosolic isoforms in eukaryotes (MARS and MARS2 in humans). Because it is essential and sufficiently divergent from human cytosolic MetRS, bacterial MetRS is investigated as a potential antibiotic target.

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