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Literature summary extracted from

  • Rani, C.; Mehra, R.; Sharma, R.; Chib, R.; Wazir, P.; Nargotra, A.; Khan, I.A.
    High-throughput screen identifies small molecule inhibitors targeting acetyltransferase activity of Mycobacterium tuberculosis GlmU (2015), Tuberculosis, 95, 664-677.
    View publication on PubMed

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.3.1.157 gene glmU, recombinant expression of His-tagged enzyme in Escherichia coli strain BL21(DE3) Mycobacterium tuberculosis
2.7.7.23 gene glmU, recombinant expression of His-tagged enzyme in Escherichia coli strain BL21(DE3) Mycobacterium tuberculosis

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.3.1.157 (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
2.3.1.157 (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
2.3.1.157 (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
2.3.1.157 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
2.3.1.157 EDTA
-
 Mycobacterium tuberculosis
2.3.1.157 additional information high-throughput screen identifies small molecule inhibitors targeting acetyltransferase activity of Mycobacterium tuberculosis GlmU, molecular docking studies, overview Mycobacterium tuberculosis
2.7.7.23 EDTA
-
 Mycobacterium tuberculosis
2.7.7.23 additional information no inhibition by 6624116, 5655606, 5810599, and 6012954 Mycobacterium tuberculosis

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.3.1.157 additional information
-
 additional information Michaelis-Menten kinetics Mycobacterium tuberculosis
2.3.1.157 0.107
-
 alpha-D-glucosamine 1-phosphate pH 7.5, 37°C, recombinant enzyme Mycobacterium tuberculosis
2.3.1.157 0.107
-
 alpha-D-glucosamine 1-phosphate pH not specified in the publication, temperature not specified in the publication Mycobacterium tuberculosis
2.3.1.157 0.23
-
 acetyl-CoA pH 7.5, 37°C, recombinant enzyme Mycobacterium tuberculosis
2.3.1.157 0.23
-
 acetyl-CoA pH not specified in the publication, temperature not specified in the publication Mycobacterium tuberculosis
2.7.7.23 additional information
-
 additional information Michaelis-Menten kinetics Mycobacterium tuberculosis
2.7.7.23 0.03
-
 UTP pH 7.5, 37°C, recombinant enzyme Mycobacterium tuberculosis
2.7.7.23 0.041
-
 N-acetyl-alpha-D-glucosamine 1-phosphate pH 7.5, 37°C, recombinant enzyme Mycobacterium tuberculosis

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.3.1.157 Mg2+ required Mycobacterium tuberculosis
2.7.7.23 Mg2+ required Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.3.1.157 acetyl-CoA + alpha-D-glucosamine 1-phosphate Mycobacterium tuberculosis
-
 CoA + N-acetyl-alpha-D-glucosamine 1-phosphate
-
 ?
2.3.1.157 acetyl-CoA + alpha-D-glucosamine 1-phosphate Mycobacterium tuberculosis H37Rv
-
 CoA + N-acetyl-alpha-D-glucosamine 1-phosphate
-
 ?
2.3.1.157 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 ?
-
 ?
2.3.1.157 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 ?
-
 ?
2.7.7.23 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 ?
-
 ?
2.7.7.23 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 ?
-
 ?
2.7.7.23 UTP + N-acetyl-alpha-D-glucosamine 1-phosphate Mycobacterium tuberculosis
-
 diphosphate + UDP-N-acetyl-alpha-D-glucosamine
-
 ?
2.7.7.23 UTP + N-acetyl-alpha-D-glucosamine 1-phosphate Mycobacterium tuberculosis H37Rv
-
 diphosphate + UDP-N-acetyl-alpha-D-glucosamine
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.3.1.157 Mycobacterium tuberculosis
-
-
-
2.3.1.157 Mycobacterium tuberculosis P9WMN3
-
-
2.3.1.157 Mycobacterium tuberculosis H37Rv P9WMN3
-
-
2.7.7.23 Mycobacterium tuberculosis P9WMN3
-
-
2.7.7.23 Mycobacterium tuberculosis H37Rv P9WMN3
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
2.3.1.157 recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and dialysis Mycobacterium tuberculosis
2.7.7.23 recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and dialysis Mycobacterium tuberculosis

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.1.157 acetyl-CoA + alpha-D-glucosamine 1-phosphate
-
 Mycobacterium tuberculosis CoA + N-acetyl-alpha-D-glucosamine 1-phosphate
-
 ?
2.3.1.157 acetyl-CoA + alpha-D-glucosamine 1-phosphate
-
 Mycobacterium tuberculosis H37Rv CoA + N-acetyl-alpha-D-glucosamine 1-phosphate
-
 ?
2.3.1.157 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 ?
-
 ?
2.3.1.157 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 ?
-
 ?
2.7.7.23 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 ?
-
 ?
2.7.7.23 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 ?
-
 ?
2.7.7.23 UTP + N-acetyl-alpha-D-glucosamine 1-phosphate
-
 Mycobacterium tuberculosis diphosphate + UDP-N-acetyl-alpha-D-glucosamine
-
 ?
2.7.7.23 UTP + N-acetyl-alpha-D-glucosamine 1-phosphate
-
 Mycobacterium tuberculosis H37Rv diphosphate + UDP-N-acetyl-alpha-D-glucosamine
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.3.1.157 GlmU
-
 Mycobacterium tuberculosis
2.7.7.23 GlmU
-
 Mycobacterium tuberculosis

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.3.1.157 37
-
 assay at Mycobacterium tuberculosis
2.7.7.23 37
-
 assay at Mycobacterium tuberculosis

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.3.1.157 7.5
-
 assay at Mycobacterium tuberculosis
2.7.7.23 7.5
-
 assay at Mycobacterium tuberculosis

Cofactor

EC Number Cofactor Comment Organism Structure
2.3.1.157 acetyl-CoA
-
 Mycobacterium tuberculosis
2.7.7.23 acetyl-CoA
-
 Mycobacterium tuberculosis

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
2.3.1.157 additional information
-
 additional information inhibition kinetics, overview Mycobacterium tuberculosis
2.3.1.157 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
2.3.1.157 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
2.3.1.157 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
2.3.1.157 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

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
2.3.1.157 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
2.3.1.157 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
2.3.1.157 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
2.3.1.157 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
2.3.1.157 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
2.3.1.157 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
2.3.1.157 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
2.3.1.157 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
2.3.1.157 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
2.3.1.157 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

EC Number General Information Comment Organism
2.3.1.157 metabolism the enzymeis involved in the UDP-N-acetylglucosamine synthesis pathway, overview Mycobacterium tuberculosis
2.3.1.157 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
2.7.7.23 metabolism the enzymeis involved in the UDP-N-acetylglucosamine synthesis pathway, overview Mycobacterium tuberculosis
2.7.7.23 physiological function N-acetylglucosamine-1-phosphate uridyltransferase (GlmU) is a pivotal bifunctional enzyme, its N- and C-terminal domains catalyze 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