Methionyl-tRNA synthetase (Staphylococcus aureus) (MetRS)

Methionyl-tRNA synthetase (MetRS) is an essential enzyme in Staphylococcus aureus that catalyzes the attachment of methionine to its cognate tRNA molecule, a prerequisite for protein biosynthesis [UniProt: P0A028]. This enzyme belongs to the Class I family of aminoacyl-tRNA synthetases and is vital for both the initiation and elongation phases of translation [PubMed: 15659343]. Because bacterial MetRS is structurally distinct from the human cytoplasmic version, it represents a high-value target for the development of narrow-spectrum antibiotics [PubMed: 19153077]. Inhibition of MetRS prevents the formation of methionyl-tRNA, leading to the arrest of protein synthesis and subsequent bacterial cell death [PubMed: 22437630]. Therapeutic candidates such as REP8839 have demonstrated potent activity against S. aureus, including methicillin-resistant (MRSA) and mupirocin-resistant strains [PubMed: 19153077]. However, a primary challenge in targeting this enzyme is the potential for cross-reactivity with human mitochondrial MetRS and the emergence of resistance through mutations in the metG gene [PubMed: 25135315].

Other names

Methionine--tRNA ligaseMetRSMRSmetGMethionyl-tRNA ligase

Inhibition of the aminoacylation of tRNA(Met), which prevents the initiation and elongation of polypeptide chains during bacterial protein synthesis.