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Literature summary for 6.3.2.8 extracted from

  • Humnabadkar, V.; Prabhakar, K.R.; Narayan, A.; Sharma, S.; Guptha, S.; Manjrekar, P.; Chinnapattu, M.; Ramachandran, V.; Hameed, S.P.; Ravishankar, S.; Chatterji, M.
    UDP-N-acetylmuramic acid L-alanine ligase (MurC) inhibition in a tolC mutant Escherichia coli strain leads to cell death (2014), Antimicrob. Agents Chemother., 58, 6165-6171 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 6.3.2.8

Cloned(Commentary)

Cloned (Comment) Organism
gene murC, overexpression of wild-type MurC in the Escherichia coli tolC mutant Escherichia coli

Inhibitors

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

Metals/Ions Comment Organism Structure
Mg2+ required Escherichia coli
Mg2+ required Pseudomonas aeruginosa

Natural Substrates/ Products (Substrates)

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

Organism UniProt Comment Textmining
Escherichia coli
-
-
-
Pseudomonas aeruginosa
-
-
-

Substrates and Products (Substrate)

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

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 [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
 assay at Escherichia coli
25
-
 assay at Pseudomonas aeruginosa

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8
-
 assay at Escherichia coli
8
-
 assay at Pseudomonas aeruginosa

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Escherichia coli
ATP
-
 Pseudomonas aeruginosa

IC50 Value

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

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