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Literature summary for 2.5.1.7 extracted from

  • Blake, K.L.; ONeill, A.J.; Mengin-Lecreulx, D.; Henderson, P.J.; Bostock, J.M.; Dunsmore, C.J.; Simmons, K.J.; Fishwick, C.W.; Leeds, J.A.; Chopra, I.
    The nature of Staphylococcus aureus MurA and MurZ and approaches for detection of peptidoglycan biosynthesis inhibitors (2009), Mol. Microbiol., 72, 335-343.
    View publication on PubMed
Search for more literature for 2.5.1.7

Application

Application Comment Organism
drug development cell-wall synthesis is an important target for antibacterial agents, and MurA is one of the few enzymes involved in the cytoplasmic stage of peptidoglycan biosynthesis which is specifically inhibited by an existing antimicrobial agent Staphylococcus aureus

Cloned(Commentary)

Cloned (Comment) Organism
the murA gene is cloned and overexpressed in Escherichia coli with a C-terminal 6-His tag Staphylococcus aureus
the murZ gene is cloned and overexpressed in Escherichia coli with a C-terminal 6-His tag Staphylococcus aureus

Inhibitors

Inhibitors Comment Organism Structure
fosfomycin despite low level expression during normal growth, murZ expression is strongly induced up to 6fold following exposure to inhibitors of peptidoglycan biosynthesis, minimum inhibitory concentration is 4 mg/ml; the naturally occurring antibiotic, which is an analogue of phosphoenolpyruvate, irreversibly inhibits the majority of MurA enzymes, fosfomycin minimum inhibitory concentration is 8 mg/ml, peptidoglycan content is reduced by approximately 25% following inactivation of murA Staphylococcus aureus

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.01148
-
 phosphoenolpyruvate 50 mM HEPES, 250 mM methylthioguanosine, 0.1 U/ml purine-nucleoside phosphorylase, 100 mM dithiothreitol, pH 7.6 Staphylococcus aureus
0.01157
-
 phosphoenolpyruvate 50 mM HEPES, 250 mM methylthioguanosine, 0.1 U/ml purine-nucleoside phosphorylase, 100 mM dithiothreitol, pH 7.6 Staphylococcus aureus
0.1239
-
 UDP-N-acetyl-D-glucosamine 50 mM HEPES, 250 mM methylthioguanosine, 0.1 U/ml purine-nucleoside phosphorylase, 100 mM dithiothreitol, pH 7.6 Staphylococcus aureus
0.1686
-
 UDP-N-acetyl-D-glucosamine 50 mM HEPES, 250 mM methylthioguanosine, 0.1 U/ml purine-nucleoside phosphorylase, 100 mM dithiothreitol, pH 7.6 Staphylococcus aureus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine Staphylococcus aureus
-
 phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine
-
 ?

Organism

Organism UniProt Comment Textmining
Staphylococcus aureus
-
-
-

Purification (Commentary)

Purification (Comment) Organism
by using affinity chromatography Staphylococcus aureus

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
phosphoenolpyruvate + UDP-N-acetyl-D-glucosamine
-
 Staphylococcus aureus phosphate + UDP-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine
-
 ?

Synonyms

Synonyms Comment Organism
MurA
-
 Staphylococcus aureus
MurZ
-
 Staphylococcus aureus
UDP-GlcNAc enolpyruvyl transferase
-
 Staphylococcus aureus
UDP-N-acetylglucosamine enolpyruvyl transferase
-
 Staphylococcus aureus

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.76
-
 fosfomycin 50 mM HEPES, 250 mM methylthioguanosine, 0.1 U/ml purine-nucleoside phosphorylase, 100 mM dithiothreitol, pH 7.6 Staphylococcus aureus
1.13
-
 fosfomycin 50 mM HEPES, 250 mM methylthioguanosine, 0.1 U/ml purine-nucleoside phosphorylase, 100 mM dithiothreitol, pH 7.6 Staphylococcus aureus

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.00136
-
 50 mM HEPES, 250 mM methylthioguanosine, 0.1 U/ml purine-nucleoside phosphorylase, 100 mM dithiothreitol, pH 7.6 Staphylococcus aureus fosfomycin
0.00137
-
 50 mM HEPES, 250 mM methylthioguanosine, 0.1 U/ml purine-nucleoside phosphorylase, 100 mM dithiothreitol, pH 7.6 Staphylococcus aureus fosfomycin

General Information

General Information Comment Organism
physiological function enzyme catalyzes the first committed step of peptidoglycan biosynthesis Staphylococcus aureus

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
0.000005
-
 UDP-N-acetyl-D-glucosamine 50 mM HEPES, 250 mM methylthioguanosine, 0.1 U/ml purine-nucleoside phosphorylase, 100 mM dithiothreitol, pH 7.6 Staphylococcus aureus
0.000009
-
 UDP-N-acetyl-D-glucosamine 50 mM HEPES, 250 mM methylthioguanosine, 0.1 U/ml purine-nucleoside phosphorylase, 100 mM dithiothreitol, pH 7.6 Staphylococcus aureus
0.00007
-
 phosphoenolpyruvate 50 mM HEPES, 250 mM methylthioguanosine, 0.1 U/ml purine-nucleoside phosphorylase, 100 mM dithiothreitol, pH 7.6 Staphylococcus aureus
0.0001
-
 phosphoenolpyruvate 50 mM HEPES, 250 mM methylthioguanosine, 0.1 U/ml purine-nucleoside phosphorylase, 100 mM dithiothreitol, pH 7.6 Staphylococcus aureus