PMID:23462005

Citation	Han, SG, Lee, WK, Jin, BS, Lee, KI, Lee, HH and Yu, YG (2013) Identification of Novel Irreversible Inhibitors of UDP-N-Acetylglucosamine Enolpyruvyl Transferase (MurA) from Haemophilus influenzae. J. Microbiol. Biotechnol. 23:329-34
Abstract	Uridinediphospho-N-acetylglucosamine enolpyruvyl transferase (MurA, E.C. 2.5.1.7) is an essential bacterial enzyme that catalyzes the first step of the cell wall biosynthetic pathway, which involves the transfer of an enolpyruvyl group from phosphoenolpyruvate to uridinediphospho-Nacetylglucosamine. In this study, novel inhibitors of Haemophilus influenzae MurA (Hi MurA) were identified using high-throughput screening of a chemical library from the Korea Chemical Bank. The identified compounds contain a quinoline moiety and have much lower effective inhibitory concentrations (IC50) than fosfomycin, a wellknown inhibitor of MurA. These inhibitors appear to covalently modify the sulfhydryl group of the active site cysteine (C117), since the C117D mutant Hi MurA was not inhibited by these compounds and excess dithiothreitol abolished their inhibitory activities. The increased mass value of Hi MurA after treatment with the identified inhibitor further confirmed that the active-site cysteine residue of Hi MurA is covalently modified by the inhibitor.
Links	PubMed
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Significance

Gene product	Qualifier	GO Term	Evidence Code	Aspect	Notes	Status
HAEI8:MURA		GO:0008760: UDP-N-acetylglucosamine 1-carboxyvinyltransferase activity	ECO:0000315:	F	Figure 3 demonstrates the inhibitory activities on MurA and then determines the residual activity. Figure 5 demonstrates the inhibitory actions of sulfhydryl group dependent activity on the mutant phenotype.	complete CACAO 7011
HAEI8:MURA	enables	GO:0008760: UDP-N-acetylglucosamine 1-carboxyvinyltransferase activity	ECO:0000315: mutant phenotype evidence used in manual assertion	F	Seeded From UniProt	complete

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