Glutamate racemase (Streptococcus pyogenes) (MurI)

Glutamate racemase (MurI) is an essential enzyme in Streptococcus pyogenes that catalyzes the reversible racemization of L-glutamate to D-glutamate (UniProt: P0C0G1). This reaction is vital for the bacteria because D-glutamate is a necessary building block for the biosynthesis of peptidoglycan, the primary structural component of the bacterial cell wall (PubMed: 11514511). Since D-glutamate is not used in human protein synthesis and humans lack a glutamate racemase ortholog, this enzyme is considered an ideal target for the development of narrow-spectrum antibiotics (PubMed: 15103634). Inhibition of MurI prevents the formation of the peptidoglycan cross-links, leading to cell wall instability and bacterial death. This target is particularly relevant for treating S. pyogenes infections, which include common conditions like strep throat as well as severe invasive diseases such as necrotizing fasciitis and streptococcal toxic shock syndrome (PubMed: 22432285). Current drug discovery efforts focus on competitive inhibitors and transition-state analogs that bind to the enzyme's active site to block its catalytic activity (PubMed: 19435314).

Other names

MurIGlutamic acid racemaseD-glutamate racemase

Inhibition of the conversion of L-glutamate to D-glutamate, thereby disrupting the synthesis of the peptidoglycan layer and leading to bacterial cell lysis.