Application | Comment | Organism |
---|---|---|
drug development | te enzyme is required for the biosynthesis of NAD. Besides the de novo pathway for NAD synthesis, a salvage pathway exists in some organisms allowing NAD to be recycled from nicotinic acid and nicotinamide. Some pathogens such as Mycobacterium leprae and Helicobacter pylori lack this salvage pathway. The different pathways for quinolinate biosynthesis in most prokaryotes and eukaryotes, combined with the fact that the salvage pathway is absent in some pathogenic microorganisms, make enzyme NadA an ideal target in the search for specific antibacterial drugs | Escherichia coli K-12 |
drug development | te enzyme is required for the biosynthesis of NAD. Besides the de novo pathway for NAD synthesis, a salvage pathway exists in some organisms allowing NAD to be recycled from nicotinic acid and nicotinamide. Some pathogens such as Mycobacterium leprae and Helicobacter pylori lack this salvage pathway. The different pathways for quinolinate biosynthesis in most prokaryotes and eukaryotes, combined with the fact that the salvage pathway is absent in some pathogenic microorganisms, make enzyme NadA an ideal target in the search for specific antibacterial drugs | Thermotoga maritima |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
Phosphoglycolic acid | significantly inhibits the enzyme's triose phosphate isomerase activity at 1 mM | Escherichia coli K-12 | |
Phosphoglycolic acid | significantly inhibits the enzyme's triose phosphate isomerase activity at 1 mM | Thermotoga maritima |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Fe2+ | an [4Fe-4S] cluster-containing enzyme | Escherichia coli K-12 | |
Fe2+ | an [4Fe-4S] cluster-containing enzyme | Thermotoga maritima | |
[4Fe-4S] cluster | an [4Fe-4S] cluster-containing enzyme. The Fe/S cluster of NadA (both Fe4S4 and Fe2S2) might play a significant structural role in NadA that could affect the triose phosphate isomerase activity | Escherichia coli K-12 | |
[4Fe-4S] cluster | an [4Fe-4S] cluster-containing enzyme. The Fe/S cluster of NadA (both Fe4S4 and Fe2S2) might play a significant structural role in NadA that could affect the triose phosphate isomerase activity | Thermotoga maritima |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
glycerone phosphate + iminosuccinate | Escherichia coli K-12 | - |
pyridine-2,3-dicarboxylate + 2 H2O + phosphate | - |
? | |
glycerone phosphate + iminosuccinate | Thermotoga maritima | - |
pyridine-2,3-dicarboxylate + 2 H2O + phosphate | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Escherichia coli K-12 | P11458 | gene nadA | - |
Thermotoga maritima | Q9X1X7 | gene nadA | - |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
glycerone phosphate + iminosuccinate = pyridine-2,3-dicarboxylate + 2 H2O + phosphate | reaction mechanism with an early release of phosphate from dihydroxyacetone phosphate, that only, not glycerol 3-phosphate, can condense with iminoaspartate to form quinolinate. The NadA three-dimensional structure shows that there is no room in the active site to accommodate a condensation product on which the phosphate group from dihydroxyacetone phosphate is still present, overview. The enzyme has a triose phosphate isomerase activity catalyzing the reversible isomerization of glycerol 3-phosphate into dihydroxyacetone phosphate in an Fe/S-dependent manner | Escherichia coli K-12 | |
glycerone phosphate + iminosuccinate = pyridine-2,3-dicarboxylate + 2 H2O + phosphate | reaction mechanism with an early release of phosphate from dihydroxyacetone phosphate, that only, not glycerol 3-phosphate, can condense with iminoaspartate to form quinolinate. The NadA three-dimensional structure shows that there is no room in the active site to accommodate a condensation product on which the phosphate group from dihydroxyacetone phosphate is still present, overview. The enzyme has a triose phosphate isomerase activity catalyzing the reversible isomerization of glycerol 3-phosphate into dihydroxyacetone phosphate in an Fe/S-dependent manner | Thermotoga maritima |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
glycerone phosphate + iminosuccinate | - |
Escherichia coli K-12 | pyridine-2,3-dicarboxylate + 2 H2O + phosphate | - |
? | |
glycerone phosphate + iminosuccinate | - |
Thermotoga maritima | pyridine-2,3-dicarboxylate + 2 H2O + phosphate | - |
? | |
additional information | the enzyme has a triose phosphate isomerase activity catalyzing the reversible isomerization of glycerol 3-phosphate into dihydroxyacetone phosphate in an Fe/S-dependent manner. Only dihydroxyacetone phosphate can then condense with iminoaspartate to form quinolinate. If glycerol 3-phosphate is not converted to dihydroxyacetone phosphate no quinolinate can be produced. The enzyme as triose phosphate isomerase is more efficient in the direction of dihydroxyacetone phosphate production | Escherichia coli K-12 | ? | - |
? | |
additional information | the enzyme has a triose phosphate isomerase activity catalyzing the reversible isomerization of glycerol 3-phosphate into dihydroxyacetone phosphate in an Fe/S-dependent manner. Only dihydroxyacetone phosphate can then condense with iminoaspartate to form quinolinate. If glycerol 3-phosphate is not converted to dihydroxyacetone phosphate no quinolinate can be produced. The enzyme as triose phosphate isomerase is more efficient in the direction of dihydroxyacetone phosphate production | Thermotoga maritima | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
NadA | - |
Escherichia coli K-12 |
NadA | - |
Thermotoga maritima |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Escherichia coli K-12 |
37 | - |
assay at | Thermotoga maritima |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.5 | - |
assay at | Escherichia coli K-12 |
7.5 | - |
assay at | Thermotoga maritima |
General Information | Comment | Organism |
---|---|---|
physiological function | quinolinate synthase is an [4Fe-4S] cluster-containing dehydrating enzyme involved in synthesis of quinolinic acid, the universal precursor of the essential coenzyme nicotinamide adenine dinucleotide | Escherichia coli K-12 |
physiological function | quinolinate synthase is an [4Fe-4S] cluster-containing dehydrating enzyme involved in synthesis of quinolinic acid, the universal precursor of the essential coenzyme nicotinamide adenine dinucleotide | Thermotoga maritima |