Methionine--tRNA ligase (MetRS) (MetRS)

Methionine--tRNA ligase (MetRS) is an essential enzyme in Staphylococcus aureus that catalyzes the attachment of L-methionine to its cognate tRNA, a process fundamental to bacterial protein synthesis [1.4.1]. This enzyme is responsible for charging both the initiator tRNA (tRNA^fMet) and the elongator tRNA (tRNA^Met), thus playing a dual role in the initiation and elongation phases of translation [1.3.1, 1.5.1]. In S. aureus, MetRS belongs to the MetRS1 subclass, which is structurally distinct from the human cytoplasmic MetRS, providing a basis for selective toxicity [1.3.3, 1.3.4]. Inhibition of MetRS leads to the depletion of methionyl-tRNA, triggering the bacterial stringent response and ultimately halting protein production, which typically results in a bacteriostatic effect [1.2.4, 1.3.2]. Several small-molecule inhibitors, including REP8839 and MRS-2541, have been investigated for their potential to treat infections caused by multi-drug resistant Gram-positive pathogens like methicillin-resistant S. aureus (MRSA) [1.2.3, 1.3.1]. However, therapeutic development must address challenges such as potential cross-reactivity with human mitochondrial MetRS and the emergence of resistance through mutations in the metG gene [1.1.3, 1.3.3].

Other names

Methionyl-tRNA synthetaseMetSMethionyl-tRNA ligasemetGmetS

Inhibition of methionyl-tRNA synthetase, which prevents the charging of tRNA with methionine, thereby halting bacterial protein synthesis and inducing a stringent response.