Cloned (Comment) | Organism |
---|---|
gene murC, overexpression of wild-type MurC in the Escherichia coli tolC mutant | Escherichia coli |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(2R)-2-((4-[(5-tert-butyl-1-methyl-1H-pyrazol-3-yl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)-3-cyclohexylpropan-1-ol | a pyrazolopyrimidine, is a potent inhibitor of the enzyme and is active against an efflux pump mutant of Escherichia coli, but cellular activity against Escherichia coli is not observed. MIC values for (2R)-2-((4-[(5-tert-butyl-1-methyl-1H-pyrazol-3-yl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)-3-cyclohexylpropan-1-ol are 0.2 mM for wild-type Escherichia coli and 0.0125 for Escherichia coli tolC mutant | Escherichia coli | |
(2R)-2-((4-[(5-tert-butyl-1-methyl-1H-pyrazol-3-yl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)-3-cyclohexylpropan-1-ol | a pyrazolopyrimidine, is a potent inhibitor of the enzyme and is active against an efflux pump mutant of Pseudomonas aeruginosa, but cellular activity against Pseudomonas aeruginosa is not observed. MIC values for (2R)-2-((4-[(5-tert-butyl-1-methyl-1H-pyrazol-3-yl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)-3-cyclohexylpropan-1-ol are over 0.2 mM for wild-type Pseudomonas aeruginosa and 0.0065 mM against the Pseudomonas aeruginosa mutant strain DELTAmexADCDXY | Pseudomonas aeruginosa |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required | Escherichia coli | |
Mg2+ | required | Pseudomonas aeruginosa |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + UDP-N-acetyl-alpha-D-muramate + L-alanine | Escherichia coli | - |
ADP + phosphate + UDP-N-acetyl-alpha-D-muramoyl-L-alanine | - |
? | |
ATP + UDP-N-acetyl-alpha-D-muramate + L-alanine | Pseudomonas aeruginosa | - |
ADP + phosphate + UDP-N-acetyl-alpha-D-muramoyl-L-alanine | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Escherichia coli | - |
- |
- |
Pseudomonas aeruginosa | - |
- |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + UDP-N-acetyl-alpha-D-muramate + L-alanine | - |
Escherichia coli | ADP + phosphate + UDP-N-acetyl-alpha-D-muramoyl-L-alanine | - |
? | |
ATP + UDP-N-acetyl-alpha-D-muramate + L-alanine | - |
Pseudomonas aeruginosa | ADP + phosphate + UDP-N-acetyl-alpha-D-muramoyl-L-alanine | - |
? | |
ATP + UDP-N-acetyl-alpha-D-muramate + L-alanine | determination by phosphate detection using malachite green reagent | Escherichia coli | ADP + phosphate + UDP-N-acetyl-alpha-D-muramoyl-L-alanine | - |
? | |
ATP + UDP-N-acetyl-alpha-D-muramate + L-alanine | determination by phosphate detection using malachite green reagent | Pseudomonas aeruginosa | ADP + phosphate + UDP-N-acetyl-alpha-D-muramoyl-L-alanine | - |
? |
Synonyms | Comment | Organism |
---|---|---|
MurC | - |
Escherichia coli |
MurC | - |
Pseudomonas aeruginosa |
UDP-N-acetylmuramic acid L-alanine ligase | - |
Escherichia coli |
UDP-N-acetylmuramic acid L-alanine ligase | - |
Pseudomonas aeruginosa |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
25 | - |
assay at | Escherichia coli |
25 | - |
assay at | Pseudomonas aeruginosa |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
8 | - |
assay at | Escherichia coli |
8 | - |
assay at | Pseudomonas aeruginosa |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Escherichia coli | |
ATP | - |
Pseudomonas aeruginosa |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.0000007 | - |
pH 8.0, 25°C, recombinant enzyme | Pseudomonas aeruginosa | (2R)-2-((4-[(5-tert-butyl-1-methyl-1H-pyrazol-3-yl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)-3-cyclohexylpropan-1-ol | |
0.000012 | - |
pH 8.0, 25°C, recombinant enzyme | Escherichia coli | (2R)-2-((4-[(5-tert-butyl-1-methyl-1H-pyrazol-3-yl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)-3-cyclohexylpropan-1-ol |
General Information | Comment | Organism |
---|---|---|
malfunction | UDP-N-acetylmuramic acid L-alanine ligase (MurC) inhibition in a tolC mutant Escherichia coli strain leads to cell death. The mutant strain shows accumulation of the MurC substrate and a decrease in the level of product upon treatment with (2R)-2-((4-[(5-tert-butyl-1-methyl-1H-pyrazol-3-yl)amino]-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)-3-cyclohexylpropan-1-ol, indicating inhibition of MurC enzyme in these cells. Overexpression of wild-type MurC in the Escherichia coli tolC mutant leads to an increase in the compound A MIC by over 16fold, establishing a correlation between MurC inhibition and cellular activity | Escherichia coli |