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Literature summary for 2.3.1.157 extracted from
- High-throughput screen identifies small molecule inhibitors targeting acetyltransferase activity of Mycobacterium tuberculosis GlmU (2015), Tuberculosis, 95, 664-677.
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| gene glmU, recombinant expression of His-tagged enzyme in Escherichia coli strain BL21(DE3) | Mycobacterium tuberculosis |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| (5E)-1-(3,5-dimethylphenyl)-5-(furan-2-ylmethylidene)pyrimidine-2,4,6(1H,3H,5H)-trione | uncompetitive versus acetyl-CoA and alpha-D-glucosamine 1-phosphate, inhibits GlmU enzyme acetyltransferase activity | Mycobacterium tuberculosis |  |
| (5Z)-2-imino-5-[(2E)-3-(5-nitrofuran-2-yl)prop-2-en-1-ylidene]-1,3-thiazolidin-4-one | competitive versus acetyl-CoA, uncompetitive versus alpha-D-glucosamine 1-phosphate, specificly inhibits GlmU acetyltransferase activity and also exhibits whole cell activity against drug susceptible as well as drug resistant Mycobacterium tuberculosis. The compound also exhibits increased anti-tuberculois activity when tested in combination with rifampicin, isoniazid and ethambutol, but is cytotoxxic for the eukaryotic cell line; specific inhibition of acetyltransferase activity, competitive with respect to acetyl-CoA. Compound also exhibits whole cell activity against drug susceptible as well as drug resistant Mycobacterium tuberculosis and increased anti-TB activity when tested in combination with rifampicin, isoniazid and ethambutol. Compound is cytotoxic to eukaryotic cell line | Mycobacterium tuberculosis | |
| (5Z)-5-(furan-3-ylmethylidene)-1-(4-methoxyphenyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione | uncompetitive versus acetyl-CoA and alpha-D-glucosamine 1-phosphate, inhibits GlmU enzyme acetyltransferase activity | Mycobacterium tuberculosis | |
| 4-[[(2,6-dimethoxybenzoyl)oxy]imino]cyclohexa-2,5-dien-1-one | competitive versus acetyl-CoA, noncompetitive versus alpha-D-glucosamine 1-phosphate, specificly inhibits GlmU acetyltransferase activity and also exhibits whole cell activity against drug susceptible as well as drug resistant Mycobacterium tuberculosis. The compound also exhibits increased anti-tuberculois activity when tested in combination with rifampicin, isoniazid and ethambutol; specific inhibition of acetyltransferase activity, competitive with respect to acetyl-CoA. Compound also exhibits whole cell activity against drug susceptible as well as drug resistant Mycobacterium tuberculosis and increased anti-TB activity when tested in combination with rifampicin, isoniazid and ethambutol | Mycobacterium tuberculosis | |
| EDTA | - |
Mycobacterium tuberculosis | |
| additional information | high-throughput screen identifies small molecule inhibitors targeting acetyltransferase activity of Mycobacterium tuberculosis GlmU, molecular docking studies, overview | Mycobacterium tuberculosis |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | Michaelis-Menten kinetics | Mycobacterium tuberculosis | |
| 0.107 | - |
alpha-D-glucosamine 1-phosphate | pH 7.5, 37°C, recombinant enzyme | Mycobacterium tuberculosis | |
| 0.107 | - |
alpha-D-glucosamine 1-phosphate | pH not specified in the publication, temperature not specified in the publication | Mycobacterium tuberculosis | |
| 0.23 | - |
acetyl-CoA | pH 7.5, 37°C, recombinant enzyme | Mycobacterium tuberculosis | |
| 0.23 | - |
acetyl-CoA | pH not specified in the publication, temperature not specified in the publication | Mycobacterium tuberculosis | |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | required | Mycobacterium tuberculosis | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| acetyl-CoA + alpha-D-glucosamine 1-phosphate | Mycobacterium tuberculosis | - |
CoA + N-acetyl-alpha-D-glucosamine 1-phosphate | - |
? | |
| acetyl-CoA + alpha-D-glucosamine 1-phosphate | Mycobacterium tuberculosis H37Rv | - |
CoA + N-acetyl-alpha-D-glucosamine 1-phosphate | - |
? | |
| additional information | Mycobacterium tuberculosis | N-acetylglucosamine-1-phosphate uridyltransferase (GlmU) is a pivotal bifunctional enzyme, its N- and C-terminal domains catalyzes uridyltransferase, EC 2.7.7.23, and acetyltransferase, EC 2.3.1.157, activities, respectively | ? | - |
? | |
| additional information | Mycobacterium tuberculosis H37Rv | N-acetylglucosamine-1-phosphate uridyltransferase (GlmU) is a pivotal bifunctional enzyme, its N- and C-terminal domains catalyzes uridyltransferase, EC 2.7.7.23, and acetyltransferase, EC 2.3.1.157, activities, respectively | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Mycobacterium tuberculosis | - |
- |
- |
| Mycobacterium tuberculosis | P9WMN3 | - |
- |
| Mycobacterium tuberculosis H37Rv | P9WMN3 | - |
- |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and dialysis | Mycobacterium tuberculosis |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| acetyl-CoA + alpha-D-glucosamine 1-phosphate | - |
Mycobacterium tuberculosis | CoA + N-acetyl-alpha-D-glucosamine 1-phosphate | - |
? | |
| acetyl-CoA + alpha-D-glucosamine 1-phosphate | - |
Mycobacterium tuberculosis H37Rv | CoA + N-acetyl-alpha-D-glucosamine 1-phosphate | - |
? | |
| additional information | N-acetylglucosamine-1-phosphate uridyltransferase (GlmU) is a pivotal bifunctional enzyme, its N- and C-terminal domains catalyzes uridyltransferase, EC 2.7.7.23, and acetyltransferase, EC 2.3.1.157, activities, respectively | Mycobacterium tuberculosis | ? | - |
? | |
| additional information | N-acetylglucosamine-1-phosphate uridyltransferase (GlmU) is a pivotal bifunctional enzyme, its N- and C-terminal domains catalyzes uridyltransferase, EC 2.7.7.23, and acetyltransferase, EC 2.3.1.157, activities, respectively | Mycobacterium tuberculosis H37Rv | ? | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| GlmU | - |
Mycobacterium tuberculosis |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 37 | - |
assay at | Mycobacterium tuberculosis |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7.5 | - |
assay at | Mycobacterium tuberculosis |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| acetyl-CoA | - |
Mycobacterium tuberculosis | |
Ki Value [mM]
| Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | inhibition kinetics, overview | Mycobacterium tuberculosis | |
| 0.00901 | - |
(5Z)-5-(furan-3-ylmethylidene)-1-(4-methoxyphenyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione | pH 7.5, 37°C, recombinant enzyme | Mycobacterium tuberculosis | |
| 0.0186 | - |
(5Z)-2-imino-5-[(2E)-3-(5-nitrofuran-2-yl)prop-2-en-1-ylidene]-1,3-thiazolidin-4-one | pH 7.5, 37°C, recombinant enzyme | Mycobacterium tuberculosis | |
| 0.0388 | - |
(5E)-1-(3,5-dimethylphenyl)-5-(furan-2-ylmethylidene)pyrimidine-2,4,6(1H,3H,5H)-trione | pH 7.5, 37°C, recombinant enzyme | Mycobacterium tuberculosis | |
| 0.0652 | - |
4-[[(2,6-dimethoxybenzoyl)oxy]imino]cyclohexa-2,5-dien-1-one | pH 7.5, 37°C, recombinant enzyme | Mycobacterium tuberculosis | |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.00372 | - |
versus acetyl-CoA, pH 7.5, 37°C, recombinant enzyme | Mycobacterium tuberculosis | (5Z)-5-(furan-3-ylmethylidene)-1-(4-methoxyphenyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione | |
| 0.00614 | - |
versus alpha-D-glucosamine 1-phosphate, pH 7.5, 37°C, recombinant enzyme | Mycobacterium tuberculosis | (5Z)-5-(furan-3-ylmethylidene)-1-(4-methoxyphenyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione | |
| 0.01413 | - |
versus acetyl-CoA, pH 7.5, 37°C, recombinant enzyme | Mycobacterium tuberculosis | (5E)-1-(3,5-dimethylphenyl)-5-(furan-2-ylmethylidene)pyrimidine-2,4,6(1H,3H,5H)-trione | |
| 0.018 | - |
pH not specified in the publication, temperature not specified in the publication | Mycobacterium tuberculosis | (5Z)-2-imino-5-[(2E)-3-(5-nitrofuran-2-yl)prop-2-en-1-ylidene]-1,3-thiazolidin-4-one | |
| 0.02212 | - |
versus alpha-D-glucosamine 1-phosphate, pH 7.5, 37°C, recombinant enzyme | Mycobacterium tuberculosis | (5E)-1-(3,5-dimethylphenyl)-5-(furan-2-ylmethylidene)pyrimidine-2,4,6(1H,3H,5H)-trione | |
| 0.0318 | - |
versus acetyl-CoA, pH 7.5, 37°C, recombinant enzyme | Mycobacterium tuberculosis | (5Z)-2-imino-5-[(2E)-3-(5-nitrofuran-2-yl)prop-2-en-1-ylidene]-1,3-thiazolidin-4-one | |
| 0.0322 | - |
versus alpha-D-glucosamine 1-phosphate, pH 7.5, 37°C, recombinant enzyme | Mycobacterium tuberculosis | 4-[[(2,6-dimethoxybenzoyl)oxy]imino]cyclohexa-2,5-dien-1-one | |
| 0.0425 | - |
versus alpha-D-glucosamine 1-phosphate, pH 7.5, 37°C, recombinant enzyme | Mycobacterium tuberculosis | (5Z)-2-imino-5-[(2E)-3-(5-nitrofuran-2-yl)prop-2-en-1-ylidene]-1,3-thiazolidin-4-one | |
| 0.0533 | - |
versus acetyl-CoA, pH 7.5, 37°C, recombinant enzyme | Mycobacterium tuberculosis | 4-[[(2,6-dimethoxybenzoyl)oxy]imino]cyclohexa-2,5-dien-1-one | |
| 0.065 | - |
pH not specified in the publication, temperature not specified in the publication | Mycobacterium tuberculosis | 4-[[(2,6-dimethoxybenzoyl)oxy]imino]cyclohexa-2,5-dien-1-one | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| metabolism | the enzymeis involved in the UDP-N-acetylglucosamine synthesis pathway, overview | Mycobacterium tuberculosis |
| physiological function | N-acetylglucosamine-1-phosphate uridyltransferase (GlmU) is a pivotal bifunctional enzyme, its N- and C-terminal domains catalyzes uridyltransferase, EC 2.7.7.23, and acetyltransferase, EC 2.3.1.157, activities, respectively. Final product of GlmU catalyzed reaction, uridine-diphospho-N-acetylglucosamine (UDP-GlcNAc), acts as sugar donor providing GlcNAc residues in the synthesis of peptidoglycan and a disaccharide linker (D-N-GlcNAc-1-rhamnose), the key structural components of Mycobacterium tuberculosis cell wall | Mycobacterium tuberculosis |
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