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Literature summary for 2.3.1.157 extracted from
- Depletion of M. tuberculosis GlmU from infected murine lungs effects the clearance of the pathogen (2015), PLoS Pathog., 11, e1005235.
Application
| Application | Comment | Organism |
|---|---|---|
| medicine | GlmUMtb is a strong candidate for intervention measures against established tuberculosis infections | Mycobacterium tuberculosis |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
- |
Mycobacterium tuberculosis |
| gene glmU, recombinant expression of N-terminally FLAG-tagged enzyme | Mycobacterium tuberculosis |
Crystallization (Commentary)
| Crystallization (Comment) | Organism |
|---|---|
| docking surface representation of the GlmU allosteric site in complex with inhibitor (4Z)-4-(4-benzyloxybenzylidene)-2-(naphthalen-2-yl)-1,3-oxazol-5(4H)-one. Residues Tyr150, Glu250 and Arg 253 are in hydrogen bonding with carbonyl oxygen over the oxazole ring. Leu144, Pro147, Phe148, Tyr150, Ala233, Ala236 and Leu247 participate in strong hydrophobic interactions | Mycobacterium tuberculosis |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| (4Z)-4-(4-benzyloxybenzylidene)-2-(naphthalen-2-yl)-1,3-oxazol-5(4H)-one | a oxazolidine derivative that specifically inhibits GlmU. Administration to infected mice results in significant decrease in the bacillary load | Mycobacterium tuberculosis |  |
| 4-(4-(benzyloxy)benzylidene)-2-(naphthalen-1-yl)oxazol-5(4H)-one | i.e. Oxa33, syntesis of a specific GlmU inhibitor, molecular docking study, the inhibitor binds to an allosteric site of the uridyltransferase domain., overview. Oxa33 fails to inhibit cell growth even at concentrations as high as 0.150 mM | 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 | - |
? | |
| acetyl-CoA + alpha-D-glucosamine 1-phosphate | Mycobacterium tuberculosis ATCC 25618 | - |
CoA + N-acetyl-alpha-D-glucosamine 1-phosphate | - |
? | |
| additional information | Mycobacterium tuberculosis | the N-acetylglucosamine-1-phosphate-uridyltransferase/glucosamine-1-phosphate-acetyltransferase (GlmU) enzyme is a bifunctional enzyme with both acetyltransferase and uridylyltransferase (pyrophosphorylase) activities, catalyzing the reactions of EC 2.3.1.157, N-acetylglucosamine-1-phosphate uridyltransferase, and 2.7.7.23, UDP-N-acetylglucosamine diphosphorylase. The synthesis of the two metabolic intermediates N-acetylglucosamine-1-phosphate (GlcNAc-1-P) and UDP-GlcNAc is catalyzed by the C- and N-terminal domains, respectively | ? | - |
? | |
| additional information | Mycobacterium tuberculosis H37Rv | the N-acetylglucosamine-1-phosphate-uridyltransferase/glucosamine-1-phosphate-acetyltransferase (GlmU) enzyme is a bifunctional enzyme with both acetyltransferase and uridylyltransferase (pyrophosphorylase) activities, catalyzing the reactions of EC 2.3.1.157, N-acetylglucosamine-1-phosphate uridyltransferase, and 2.7.7.23, UDP-N-acetylglucosamine diphosphorylase. The synthesis of the two metabolic intermediates N-acetylglucosamine-1-phosphate (GlcNAc-1-P) and UDP-GlcNAc is catalyzed by the C- and N-terminal domains, respectively | ? | - |
? | |
| additional information | Mycobacterium tuberculosis ATCC 25618 | the N-acetylglucosamine-1-phosphate-uridyltransferase/glucosamine-1-phosphate-acetyltransferase (GlmU) enzyme is a bifunctional enzyme with both acetyltransferase and uridylyltransferase (pyrophosphorylase) activities, catalyzing the reactions of EC 2.3.1.157, N-acetylglucosamine-1-phosphate uridyltransferase, and 2.7.7.23, UDP-N-acetylglucosamine diphosphorylase. The synthesis of the two metabolic intermediates N-acetylglucosamine-1-phosphate (GlcNAc-1-P) and UDP-GlcNAc is catalyzed by the C- and N-terminal domains, respectively | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Mycobacterium tuberculosis | P9WMN3 | - |
- |
| Mycobacterium tuberculosis ATCC 25618 | P9WMN3 | - |
- |
| Mycobacterium tuberculosis H37Rv | P9WMN3 | - |
- |
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 | - |
? | |
| acetyl-CoA + alpha-D-glucosamine 1-phosphate | - |
Mycobacterium tuberculosis ATCC 25618 | CoA + N-acetyl-alpha-D-glucosamine 1-phosphate | - |
? | |
| additional information | the N-acetylglucosamine-1-phosphate-uridyltransferase/glucosamine-1-phosphate-acetyltransferase (GlmU) enzyme is a bifunctional enzyme with both acetyltransferase and uridylyltransferase (pyrophosphorylase) activities, catalyzing the reactions of EC 2.3.1.157, N-acetylglucosamine-1-phosphate uridyltransferase, and 2.7.7.23, UDP-N-acetylglucosamine diphosphorylase. The synthesis of the two metabolic intermediates N-acetylglucosamine-1-phosphate (GlcNAc-1-P) and UDP-GlcNAc is catalyzed by the C- and N-terminal domains, respectively | Mycobacterium tuberculosis | ? | - |
? | |
| additional information | the N-acetylglucosamine-1-phosphate-uridyltransferase/glucosamine-1-phosphate-acetyltransferase (GlmU) enzyme is a bifunctional enzyme with both acetyltransferase and uridylyltransferase (pyrophosphorylase) activities, catalyzing the reactions of EC 2.3.1.157, N-acetylglucosamine-1-phosphate uridyltransferase, and 2.7.7.23, UDP-N-acetylglucosamine diphosphorylase. The synthesis of the two metabolic intermediates N-acetylglucosamine-1-phosphate (GlcNAc-1-P) and UDP-GlcNAc is catalyzed by the C- and N-terminal domains, respectively | Mycobacterium tuberculosis H37Rv | ? | - |
? | |
| additional information | the N-acetylglucosamine-1-phosphate-uridyltransferase/glucosamine-1-phosphate-acetyltransferase (GlmU) enzyme is a bifunctional enzyme with both acetyltransferase and uridylyltransferase (pyrophosphorylase) activities, catalyzing the reactions of EC 2.3.1.157, N-acetylglucosamine-1-phosphate uridyltransferase, and 2.7.7.23, UDP-N-acetylglucosamine diphosphorylase. The synthesis of the two metabolic intermediates N-acetylglucosamine-1-phosphate (GlcNAc-1-P) and UDP-GlcNAc is catalyzed by the C- and N-terminal domains, respectively | Mycobacterium tuberculosis ATCC 25618 | ? | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| GlmU | - |
Mycobacterium tuberculosis |
| Rv1018c | - |
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 |
|---|---|---|---|
| 7.4 | - |
assay at | Mycobacterium tuberculosis |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| acetyl-CoA | - |
Mycobacterium tuberculosis | |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.099 | - |
30°C, pH not specified in the publication | Mycobacterium tuberculosis | (4Z)-4-(4-benzyloxybenzylidene)-2-(naphthalen-2-yl)-1,3-oxazol-5(4H)-one | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | GlmUMtb depletion perturbs cell wall structure and affects the bacterial survival in normoxia, overview | Mycobacterium tuberculosis |
| physiological function | absence of GlmU leads to extensive perturbation of bacterial morphology and substantial reduction in cell wall thickness under normoxic as well as hypoxic conditions. The acetyl- and uridyl-transferase activities of GlmU are independently essential for bacterial survival in vitro, and GlmU is also essential for mycobacterial survival in THP-1 cells as well as in guinea pigs. Depletion of GlmU from infected murine lungs, four weeks post infection, leads to significant reduction in the bacillary load | Mycobacterium tuberculosis |
| physiological function | the acetyl- and uridyltransferase activities of GlmUMtb are independently essential for bacterial survival in vitro, and GlmUMtb is also essential for mycobacterial survival in THP-1 cells as well as in guinea pigs. The administration of Oxa33, a novel oxazolidine derivative that specifically inhibits GlmUMtb, to infected mice results in significant decrease in the bacillary load. The synthesis of the two metabolic intermediates N-acetylglucosamine-1-phosphate (GlcNAc-1-P) and UDP-GlcNAc is catalyzed by the C- and N-terminal domains, respectively | Mycobacterium tuberculosis |
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