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Literature summary extracted from

  • Tran, A.T.; Wen, D.; West, N.P.; Baker, E.N.; Britton, W.J.; Payne, R.J.
    Inhibition studies on Mycobacterium tuberculosis N-acetylglucosamine-1-phosphate uridyltransferase (GlmU) (2013), Org. Biomol. Chem., 11, 8113-8126.
    View publication on PubMed

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.7.7.23 (2S,4R)-N-(4-((6,7-dimethoxyquinazolin-4-yl)amino)phenyl)-4-hydroxypyrrolidine-2-carboxamide
-
 Mycobacterium tuberculosis
2.7.7.23 (3-hydroxyphenyl)[4-(5,6,7,8-tetrahydroquinazolin-4-ylamino)phenyl]methanone 30% inhibition at 0.05 mM Mycobacterium tuberculosis
2.7.7.23 (4-(6,7-dimethoxyquinazolin-4-yl)piperazin-1-yl)(phenyl)-methanone
-
 Mycobacterium tuberculosis
2.7.7.23 (S)-N-(4-((6,7-dimethoxyquinazolin-4-yl)amino)phenyl)pyrrolidine-2-carboxamide
-
 Mycobacterium tuberculosis
2.7.7.23 1-(3-hydroxybenzoyl)-4-(thieno[3,2-d]pyrimidin-4-ylamino)pyridinium 38% inhibition at 0.05 mM Mycobacterium tuberculosis
2.7.7.23 2-(3-((4-((6,7-dimethoxyquinazolin-4-yl)amino)phenyl)carbamoyl)phenoxy)acetic acid 34% inhibition at 0.05 mM Mycobacterium tuberculosis
2.7.7.23 2-amino-N-(4-((6,7-dimethoxyquinazolin-4-yl)amino)phenyl)-benzamide 16% inhibition at 0.05 mM Mycobacterium tuberculosis
2.7.7.23 3-(cyanomethoxy)-N-(4-((6,7-dimethoxyquinazolin-4-yl)amino)-phenyl)benzamide
-
 Mycobacterium tuberculosis
2.7.7.23 3-amino-N-(4-((6,7-dimethoxyquinazolin-4-yl)amino)phenyl)-benzamide 17% inhibition at 0.05 mM Mycobacterium tuberculosis
2.7.7.23 5'-deoxy-5'-[[4-(3,4-dihydroxyphenyl)-1,3-thiazol-2-yl]amino]uridine 37% inhibition at 2 mM Mycobacterium tuberculosis
2.7.7.23 5'-[N-[2-[[2-(acetylamino)-2-deoxy-D-glucopyranosyl]oxy]acetyl]sulfamoyl]uridine 55% inhibition at 2 mM Mycobacterium tuberculosis
2.7.7.23 5'-[[2-(cyclohexylamino)-2-oxoethyl](2,3-dihydroxybenzoyl)amino]-5'-deoxyuridine 10% inhibition at 2 mM Mycobacterium tuberculosis
2.7.7.23 5'-[[N-[2-[[2-(acetylamino)-2-deoxy-alpha-D-glucopyranosyl]oxy]acetyl]-L-alpha-aspartyl-L-alpha-aspartyl]amino]-5'-deoxyuridine 60% inhibition at 2 mM Mycobacterium tuberculosis
2.7.7.23 6,7-dimethoxy-4-(piperazin-1-yl)quinazoline
-
 Mycobacterium tuberculosis
2.7.7.23 9H-fluoren-9-ylmethyl (2S)-2-([4-[(6,7-dimethoxyquinazolin-4-yl)amino]phenyl]carbamoyl)pyrrolidine-1-carboxylate
-
 Mycobacterium tuberculosis
2.7.7.23 9H-fluoren-9-ylmethyl (2S)-2-[(4-aminophenyl)carbamoyl]pyrrolidine-1-carboxylate
-
 Mycobacterium tuberculosis
2.7.7.23 cyclohexyl(4-(6,7-dimethoxyquinazolin-4-yl)piperazin-1-yl)-methanone
-
 Mycobacterium tuberculosis
2.7.7.23 additional information design of bisubstrate and transition-state based inhibitors of GlmU uridyltransferase, the potential inhibitors against GlmU are initially prepared leading to the discovery of active minoquinazoline-based compounds with inhibitory potential against the uridyltransferase activity, compound synthesis, overview. No inhibition by 10, 11, 15, 16, 17, 32, and 34 Mycobacterium tuberculosis
2.7.7.23 N-(2-((6,7-dimethoxyquinazolin-4-yl)amino)cyclohexyl)benzamide
-
 Mycobacterium tuberculosis
2.7.7.23 N-(2-((6,7-dimethoxyquinazolin-4-yl)amino)cyclohexyl)cyclohexane carboxamide
-
 Mycobacterium tuberculosis
2.7.7.23 N-(4-((6,7-dimethoxyquinazolin-4-yl)amino)phenyl)-2-hydroxybenzamide 14% inhibition at 0.05 mM Mycobacterium tuberculosis
2.7.7.23 N-(4-((6,7-dimethoxyquinazolin-4-yl)amino)phenyl)-2-nitrobenzamide 13% inhibition at 0.05 mM Mycobacterium tuberculosis
2.7.7.23 N-(4-((6,7-dimethoxyquinazolin-4-yl)amino)phenyl)-3-(4-fluoro-phenyl)-5-methylisoxazole-4-carboxamide 19% inhibition at 0.05 mM Mycobacterium tuberculosis
2.7.7.23 N-(4-((6,7-dimethoxyquinazolin-4-yl)amino)phenyl)-3-hydroxybenzamide 35% inhibition at 0.05 mM Mycobacterium tuberculosis
2.7.7.23 N-(4-((6,7-dimethoxyquinazolin-4-yl)amino)phenyl)-3-methoxy benzamide 38% inhibition at 0.05 mM Mycobacterium tuberculosis
2.7.7.23 N-(4-((6,7-dimethoxyquinazolin-4-yl)amino)phenyl)-3-nitrobenzamide
-
 Mycobacterium tuberculosis
2.7.7.23 N-(4-((6,7-dimethoxyquinazolin-4-yl)amino)phenyl)-4-fluorobenzamide 21% inhibition at 0.05 mM Mycobacterium tuberculosis
2.7.7.23 N-(4-((6,7-dimethoxyquinazolin-4-yl)amino)phenyl)-4-hydroxybenzamide 18% inhibition at 0.05 mM Mycobacterium tuberculosis
2.7.7.23 N-(4-((6,7-dimethoxyquinazolin-4-yl)amino)phenyl)cyclohexane carboxamide 22% inhibition at 2 mM Mycobacterium tuberculosis
2.7.7.23 N-(4-((6,7-dimethoxyquinazolin-4-yl)amino)phenyl)pyrazine-2-carboxamide 19% inhibition at 0.05 mM Mycobacterium tuberculosis
2.7.7.23 N-[4-[(6,7-dimethoxyquinazolin-4-yl)amino]phenyl]benzamide 44% inhibition at 2 mM Mycobacterium tuberculosis
2.7.7.23 N-[4-[(7-hydroxy-6-methoxyquinazolin-4-yl)amino]phenyl]benzamide 36% inhibition at 2 mM Mycobacterium tuberculosis
2.7.7.23 N1-(6,7-dimethoxyquinazolin-4-yl)benzene-1,4-diamine 14% inhibition at 2 mM Mycobacterium tuberculosis
2.7.7.23 N1-(6,7-dimethoxyquinazolin-4-yl)cyclohexane-1,2-diamine
-
 Mycobacterium tuberculosis
2.7.7.23 tert-butyl (2S,4S)-2-([4-[(6,7-dimethoxyquinazolin-4-yl)amino]phenyl]carbamoyl)-4-hydroxypyrrolidine-1-carboxylate
-
 Mycobacterium tuberculosis
2.7.7.23 [4-[(6,7-dimethoxyquinazolin-4-yl)amino]phenyl](3-hydroxyphenyl)methanone 7% inhibition at 0.05 mM Mycobacterium tuberculosis

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.7.7.23 additional information
-
 additional information Michaelis-Menten kinetics Mycobacterium tuberculosis

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
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.
2.7.7.23 additional information Mycobacterium tuberculosis the bifunctional role of GlmU arises from two independent domains of the enzyme which possess acetyltransferase, EC 2.3.1.157, and uridyltransferase, EC 2.7.7.23, activities. The acetyltransferase domain, found in the C-terminus of the protein, is responsible for the first step of the reaction, in which an acetyl group is transferred from AcCoA to GlcN-1-P forming GlcNAc-1-P. GlcNAc-1-P then serves as a substrate for the uridyltransferase active site in the N-terminus of the enzyme which forms UDP-GlcNAc ?
-
 ?
2.7.7.23 additional information Mycobacterium tuberculosis H37Rv the bifunctional role of GlmU arises from two independent domains of the enzyme which possess acetyltransferase, EC 2.3.1.157, and uridyltransferase, EC 2.7.7.23, activities. The acetyltransferase domain, found in the C-terminus of the protein, is responsible for the first step of the reaction, in which an acetyl group is transferred from AcCoA to GlcN-1-P forming GlcNAc-1-P. GlcNAc-1-P then serves as a substrate for the uridyltransferase active site in the N-terminus of the enzyme which forms UDP-GlcNAc ?
-
 ?
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
2.7.7.23 Mycobacterium tuberculosis P9WMN3
-
-
2.7.7.23 Mycobacterium tuberculosis H37Rv P9WMN3
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.7.23 additional information the bifunctional role of GlmU arises from two independent domains of the enzyme which possess acetyltransferase, EC 2.3.1.157, and uridyltransferase, EC 2.7.7.23, activities. The acetyltransferase domain, found in the C-terminus of the protein, is responsible for the first step of the reaction, in which an acetyl group is transferred from AcCoA to GlcN-1-P forming GlcNAc-1-P. GlcNAc-1-P then serves as a substrate for the uridyltransferase active site in the N-terminus of the enzyme which forms UDP-GlcNAc Mycobacterium tuberculosis ?
-
 ?
2.7.7.23 additional information development of a double-enzyme-coupled continuous assay for Mycobacterium tuberculosis GlmU uridyltransferase. The assay used excess amounts of two coupling enzymes, namely inorganic pyrophosphatase (IPP) (EC 3.6.1.1) and purine nucleoside phosphorylase (PNPase) (EC 2.4.2.1) in the presence of 2-amino-6-mercapto-7-methylpurine ribonucleoside. the pyrophosphate produced by GlmU uridyltransferase is subsequently hydrolysed to phosphate by IPP. The phosphate then serves as a substrate for PNPase which catalyses the phosphorolytic cleavage of the glycosidic bond in 2-amino-6-mercapto-7-methylpurine ribonucleoside, resulting in the formation of 2-amino-6-mercapto-7-methylpurine that can be detected spectroscopically Mycobacterium tuberculosis ?
-
 ?
2.7.7.23 additional information the bifunctional role of GlmU arises from two independent domains of the enzyme which possess acetyltransferase, EC 2.3.1.157, and uridyltransferase, EC 2.7.7.23, activities. The acetyltransferase domain, found in the C-terminus of the protein, is responsible for the first step of the reaction, in which an acetyl group is transferred from AcCoA to GlcN-1-P forming GlcNAc-1-P. GlcNAc-1-P then serves as a substrate for the uridyltransferase active site in the N-terminus of the enzyme which forms UDP-GlcNAc Mycobacterium tuberculosis H37Rv ?
-
 ?
2.7.7.23 additional information development of a double-enzyme-coupled continuous assay for Mycobacterium tuberculosis GlmU uridyltransferase. The assay used excess amounts of two coupling enzymes, namely inorganic pyrophosphatase (IPP) (EC 3.6.1.1) and purine nucleoside phosphorylase (PNPase) (EC 2.4.2.1) in the presence of 2-amino-6-mercapto-7-methylpurine ribonucleoside. the pyrophosphate produced by GlmU uridyltransferase is subsequently hydrolysed to phosphate by IPP. The phosphate then serves as a substrate for PNPase which catalyses the phosphorolytic cleavage of the glycosidic bond in 2-amino-6-mercapto-7-methylpurine ribonucleoside, resulting in the formation of 2-amino-6-mercapto-7-methylpurine that can be detected spectroscopically 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
-
 ?

Temperature Optimum [°C]

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

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.7.7.23 7.6
-
 assay at Mycobacterium tuberculosis

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
2.7.7.23 0.074
-
 pH 7.6, 37°C Mycobacterium tuberculosis N-(4-((6,7-dimethoxyquinazolin-4-yl)amino)phenyl)-3-hydroxybenzamide

General Information

EC Number General Information Comment Organism
2.7.7.23 metabolism the first committed step in the biosynthesis of peptidoglycan involves the formation of uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) from uridine triphosphate (UTP) and GlcNAc-1-phosphate. This reactionis catalysed by N-acetylglucosamine-1-phosphate uridyltransferase (GlmU), a bifunctional enzyme with two independent active sites that possess acetyltransferase and uridyltransferase activities Mycobacterium tuberculosis