The bacterial cell wall represents an attractive target site for antibiotic research as it is a fundamental structure for bacterial survival. The enzyme MurA (UDP-N-acetylglucosamine enolpyruvyl transferase), accomplishes an initial step in the cytoplasmic biosynthesis of peptidoglycan precursor molecules. It catalyzes the transfer reaction of phosphoenolypyruvate (PEP) to the 3‘hydroxyl’ group of UDP-N-acetyl glucosamine (UNAG) generating enolpyruvyl-UDPN-acetyl glucosamine (EP-UNAG) and inorganic phosphate. The broad-spectrum antibiotic fosfomycin – to date still the only known MurA inhibitor with clinical relevance - acts as an analogue of the substrate PEP by irreversible alkylation of the Cys115 thiol group. The MurA-dependent metabolites are of vital importance for bacteria, and the enzyme is therefore in the focus of anti bacterial drug discovery.
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