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Literature summary for 2.7.4.22 extracted from

  • Doig, P.; Gorseth, E.; Nash, T.; Patten, A.; Gao, N.; Blackett, C.
    Screening-based discovery of the first novel ATP competitive inhibitors of the Staphylococcus aureus essential enzyme UMP kinase (2013), Biochem. Biophys. Res. Commun., 437, 162-167.
    View publication on PubMed

Application

Application Comment Organism
drug development the enzyme is found only in bacteria and is a target for the discovery of antibacterials Staphylococcus aureus

Cloned(Commentary)

Cloned (Comment) Organism
gene pyrH, recombinant expression in Escherichia coli strain BL21 (DE3) from vector pT73.3 Staphylococcus aureus

Inhibitors

Inhibitors Comment Organism Structure
1-[2-[(2-amino-6-phenylpyrimidin-4-yl)amino]phenyl]ethanone
-
Staphylococcus aureus
2-amino-8-(2-oxo-2-phenylethoxy)-1,4,5,9-tetrahydro-6H-purin-6-one 10 micromol, 60 min, room temperature, 75% inhibition, crystal enzyme complex structure, overview Staphylococcus aureus
2-amino-8-hydroxy-1,4,5,9-tetrahydro-6H-purin-6-one 10 micromol, 60 min, room temperature, 18% inhibition Staphylococcus aureus
2-amino-8-[2-(2-methylphenyl)-2-oxoethoxy]-1,4,5,9-tetrahydro-6H-purin-6-one 10 micromol, 60 min, room temperature, 48% inhibition Staphylococcus aureus
2-amino-8-[2-(3-methylphenyl)-2-oxoethoxy]-1,4,5,9-tetrahydro-6H-purin-6-one 10 micromol, 60 min, room temperature, 77% inhibition Staphylococcus aureus
2-amino-8-[2-(4-fluorophenyl)-2-oxoethoxy]-1,4,5,9-tetrahydro-6H-purin-6-one 10 micromol, 60 min, room temperature, 73% inhibition Staphylococcus aureus
2-amino-8-[2-(4-hydroxyphenyl)-2-oxoethoxy]-1,4,5,9-tetrahydro-6H-purin-6-one 10 micromol, 60 min, room temperature, 77% inhibition Staphylococcus aureus
2-amino-8-[2-(4-methoxyphenyl)-2-oxoethoxy]-1,4,5,9-tetrahydro-6H-purin-6-one 10 micromol, 60 min, room temperature, 74% inhibition Staphylococcus aureus
2-amino-8-[2-(4-methylphenyl)-2-oxoethoxy]-1,4,5,9-tetrahydro-6H-purin-6-one 10 micromol, 60 min, room temperature, 80% inhibition Staphylococcus aureus
4-[(2-amino-6-oxo-4,5,6,9-tetrahydro-1H-purin-8-yl)methyl]benzonitrile 10 micromol, 60 min, room temperature, 53% inhibition, crystal enzyme complex structure, overview Staphylococcus aureus
4-[[(2-amino-6-oxo-4,5,6,9-tetrahydro-1H-purin-8-yl)oxy]acetyl]benzonitrile 10 micromol, 60 min, room temperature, 68% inhibition Staphylococcus aureus
N4,6-diphenylpyrimidine-2,4-diamine
-
Staphylococcus aureus
N4-(2-methoxyphenyl)-6-phenylpyrimidine-2,4-diamine
-
Staphylococcus aureus
N4-(2-methylphenyl)-6-phenylpyrimidine-2,4-diamine
-
Staphylococcus aureus
N4-(3-methylphenyl)-6-phenylpyrimidine-2,4-diamine
-
Staphylococcus aureus
N4-(4-methoxyphenyl)-6-phenylpyrimidine-2,4-diamine
-
Staphylococcus aureus
N4-(4-methylphenyl)-6-phenylpyrimidine-2,4-diamine
-
Staphylococcus aureus
N4-ethyl-N4,6-diphenylpyrimidine-2,4-diamine
-
Staphylococcus aureus
N6-[(4-nitrophenyl)methyl]-N2-[[3-(trifluoromethyl)phenyl]methyl]-1H-purine-2,6-diamine
-
Staphylococcus aureus

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information steady-state kinetics, velocity curves for the enzyme fit to a steady state random Bi Bi mechanism or ordered Bi Bi mechanism. Data fits both models equally well Staphylococcus aureus
0.043
-
UMP pH 7.5, 22°C, random BiBi mechanism Staphylococcus aureus
0.086
-
UMP pH 7.5, 22°C, ordered BiBi mechanism Staphylococcus aureus
0.742
-
ATP pH 7.5, 22°C, random BiBi mechanism Staphylococcus aureus
1.485
-
ATP pH 7.5, 22°C, ordered BiBi mechanism Staphylococcus aureus

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Staphylococcus aureus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + UMP Staphylococcus aureus
-
ADP + UDP
-
r
ATP + UMP Staphylococcus aureus ATCC 601055
-
ADP + UDP
-
r

Organism

Organism UniProt Comment Textmining
Staphylococcus aureus
-
gene pyrH
-
Staphylococcus aureus ATCC 601055
-
gene pyrH
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + UMP
-
Staphylococcus aureus ADP + UDP
-
r
ATP + UMP UMP kinase catalyzes the transfer of the gamma-phosphate of ATP to UMP Staphylococcus aureus ADP + UDP
-
r
ATP + UMP
-
Staphylococcus aureus ATCC 601055 ADP + UDP
-
r
ATP + UMP UMP kinase catalyzes the transfer of the gamma-phosphate of ATP to UMP Staphylococcus aureus ATCC 601055 ADP + UDP
-
r
additional information enzyme activity detection by the coupled pyruvate kinase/lactate dehydrogenase assay, UMP kinase assay development and optimization, overview Staphylococcus aureus ?
-
?
additional information enzyme activity detection by the coupled pyruvate kinase/lactate dehydrogenase assay, UMP kinase assay development and optimization, overview Staphylococcus aureus ATCC 601055 ?
-
?

Subunits

Subunits Comment Organism
hexamer analytical ultracentrifugation Staphylococcus aureus

Synonyms

Synonyms Comment Organism
pyrH
-
Staphylococcus aureus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
22
-
assay at room temperature Staphylococcus aureus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
assay at Staphylococcus aureus

Cofactor

Cofactor Comment Organism Structure
ADP
-
Staphylococcus aureus
ATP
-
Staphylococcus aureus

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0156
-
pH 7.5, 22°C Staphylococcus aureus N4,6-diphenylpyrimidine-2,4-diamine
0.025
-
pH 7.5, 22°C Staphylococcus aureus N4-ethyl-N4,6-diphenylpyrimidine-2,4-diamine
0.1
-
above, pH 7.5, 22°C Staphylococcus aureus N4-(4-methylphenyl)-6-phenylpyrimidine-2,4-diamine
0.1
-
above, pH 7.5, 22°C Staphylococcus aureus N4-(4-methoxyphenyl)-6-phenylpyrimidine-2,4-diamine
0.1
-
above, pH 7.5, 22°C Staphylococcus aureus N4-(3-methylphenyl)-6-phenylpyrimidine-2,4-diamine
4.6
-
pH 7.5, 22°C Staphylococcus aureus 1-[2-[(2-amino-6-phenylpyrimidin-4-yl)amino]phenyl]ethanone
32.9
-
pH 7.5, 22°C Staphylococcus aureus N4-(2-methoxyphenyl)-6-phenylpyrimidine-2,4-diamine
44
-
pH 8.5, 23°C Staphylococcus aureus 2-amino-8-[2-(4-methoxyphenyl)-2-oxoethoxy]-1,4,5,9-tetrahydro-6H-purin-6-one
51
-
pH 8.5, 23°C Staphylococcus aureus 2-amino-8-[2-(3-methylphenyl)-2-oxoethoxy]-1,4,5,9-tetrahydro-6H-purin-6-one
53.8
-
pH 7.5, 22°C Staphylococcus aureus N4-(2-methylphenyl)-6-phenylpyrimidine-2,4-diamine
64
-
pH 8.5, 23°C Staphylococcus aureus 2-amino-8-[2-(4-methylphenyl)-2-oxoethoxy]-1,4,5,9-tetrahydro-6H-purin-6-one
79
-
pH 8.5, 23°C Staphylococcus aureus 2-amino-8-[2-(4-fluorophenyl)-2-oxoethoxy]-1,4,5,9-tetrahydro-6H-purin-6-one
82
-
pH 8.5, 23°C Staphylococcus aureus 2-amino-8-[2-(4-hydroxyphenyl)-2-oxoethoxy]-1,4,5,9-tetrahydro-6H-purin-6-one
88
-
pH 8.5, 23°C Staphylococcus aureus 4-[[(2-amino-6-oxo-4,5,6,9-tetrahydro-1H-purin-8-yl)oxy]acetyl]benzonitrile
139
-
pH 8.5, 23°C Staphylococcus aureus 2-amino-8-(2-oxo-2-phenylethoxy)-1,4,5,9-tetrahydro-6H-purin-6-one
243
-
pH 8.5, 23°C Staphylococcus aureus 2-amino-8-[2-(2-methylphenyl)-2-oxoethoxy]-1,4,5,9-tetrahydro-6H-purin-6-one
254
-
pH 8.5, 23°C Staphylococcus aureus 4-[(2-amino-6-oxo-4,5,6,9-tetrahydro-1H-purin-8-yl)methyl]benzonitrile

General Information

General Information Comment Organism
evolution the enzyme is a member of the NMP kinase family Staphylococcus aureus
physiological function UMP kinase is an essential enzyme found only in bacteria Staphylococcus aureus