Application | Comment | Organism |
---|---|---|
drug development | riboflavin synthase is a target for the design of potential antibiotics | Mycobacterium tuberculosis |
drug development | riboflavin synthase is a target for the design of potential antibiotics | Escherichia coli |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](m-tolyl)methanone | covalent hydrate of trifluoromethylated pyrazole | Escherichia coli | |
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](m-tolyl)methanone | covalent hydrate of trifluoromethylated pyrazole | Mycobacterium tuberculosis | |
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](o-tolyl)methanone | covalent hydrate of trifluoromethylated pyrazole | Escherichia coli | |
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](o-tolyl)methanone | covalent hydrate of trifluoromethylated pyrazole | Mycobacterium tuberculosis | |
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](p-tolyl)methanone | covalent hydrate of trifluoromethylated pyrazole | Escherichia coli | |
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](p-tolyl)methanone | covalent hydrate of trifluoromethylated pyrazole | Mycobacterium tuberculosis | |
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](m-tolyl)methanone | covalent hydrate of trifluoromethylated pyrazole | Escherichia coli | |
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](m-tolyl)methanone | covalent hydrate of trifluoromethylated pyrazole | Mycobacterium tuberculosis | |
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](o-tolyl)methanone | covalent hydrate of trifluoromethylated pyrazole | Escherichia coli | |
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](o-tolyl)methanone | covalent hydrate of trifluoromethylated pyrazole | Mycobacterium tuberculosis | |
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](p-tolyl)methanone | covalent hydrate of trifluoromethylated pyrazole | Escherichia coli | |
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](p-tolyl)methanone | covalent hydrate of trifluoromethylated pyrazole | Mycobacterium tuberculosis |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
6,7-dimethyl-8-(1-D-ribityl)lumazine | Mycobacterium tuberculosis | - |
riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine | - |
? | |
6,7-dimethyl-8-(1-D-ribityl)lumazine | Escherichia coli | - |
riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine | - |
? | |
additional information | Mycobacterium tuberculosis | final step in the biosynthesis of riboflavin, the early steps in this pathway involve the addition of a nucleophile to the lumazine that will function as the donor of the four-carbon unit and the deprotonation of the C-7 methyl group of the lumazine that will function as the acceptor of the four-carbon unit to form the anion, although the identity of the nucleophile has not been rigorously established, likely candidates include water or one of the ribityl hydroxyl groups, nucleophilic addition of an anion to an imine affords an intermediate, which tautomerizes to yield a further intermediate, elimination of the anion results in an iminium ion which is attacked intramolecularly by the enamine to produce the pentacyclic intermediate, the pentacyclic compound has been isolated and shown to be a kinetically competent intermediate, 2 sequential elimination reactions then produce the final products | ? | - |
? | |
additional information | Escherichia coli | final step in the biosynthesis of riboflavin, the early steps in this pathway involve the addition of a nucleophile to the lumazine that will function as the donor of the four-carbon unit and the deprotonation of the C-7 methyl group of the lumazine that will function as the acceptor of the four-carbon unit to form the anion, although the identity of the nucleophile has not been rigorously established, likely candidates include water or one of the ribityl hydroxyl groups, nucleophilic addition of an anion to an imine affords an intermediate, which tautomerizes to yield a further intermediate, elimination of the anion results in an iminium ion which is attacked intramolecularly by the enamine to produce the pentacyclic intermediate, the pentacyclic compound has been isolated and shown to be a kinetically competent intermediate, 2 sequential elimination reactions then produce the final products | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Escherichia coli | P0AFU8 | - |
- |
Mycobacterium tuberculosis | - |
- |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
6,7-dimethyl-8-(1-D-ribityl)lumazine | - |
Mycobacterium tuberculosis | riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine | - |
? | |
6,7-dimethyl-8-(1-D-ribityl)lumazine | - |
Escherichia coli | riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine | - |
? | |
additional information | final step in the biosynthesis of riboflavin, the early steps in this pathway involve the addition of a nucleophile to the lumazine that will function as the donor of the four-carbon unit and the deprotonation of the C-7 methyl group of the lumazine that will function as the acceptor of the four-carbon unit to form the anion, although the identity of the nucleophile has not been rigorously established, likely candidates include water or one of the ribityl hydroxyl groups, nucleophilic addition of an anion to an imine affords an intermediate, which tautomerizes to yield a further intermediate, elimination of the anion results in an iminium ion which is attacked intramolecularly by the enamine to produce the pentacyclic intermediate, the pentacyclic compound has been isolated and shown to be a kinetically competent intermediate, 2 sequential elimination reactions then produce the final products | Mycobacterium tuberculosis | ? | - |
? | |
additional information | final step in the biosynthesis of riboflavin, the early steps in this pathway involve the addition of a nucleophile to the lumazine that will function as the donor of the four-carbon unit and the deprotonation of the C-7 methyl group of the lumazine that will function as the acceptor of the four-carbon unit to form the anion, although the identity of the nucleophile has not been rigorously established, likely candidates include water or one of the ribityl hydroxyl groups, nucleophilic addition of an anion to an imine affords an intermediate, which tautomerizes to yield a further intermediate, elimination of the anion results in an iminium ion which is attacked intramolecularly by the enamine to produce the pentacyclic intermediate, the pentacyclic compound has been isolated and shown to be a kinetically competent intermediate, 2 sequential elimination reactions then produce the final products | Escherichia coli | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
riboflavin synthase | - |
Mycobacterium tuberculosis |
riboflavin synthase | - |
Escherichia coli |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
0.0067 | - |
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](o-tolyl)methanone | Ki value, mechanism is partial | Mycobacterium tuberculosis | |
0.0087 | - |
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](o-tolyl)methanone | noncompetitive mechanism, compound has a kis value of 0.0087 mM and moderate antibiotic activity against both Mycobacterium tuberculosis replicating phenotype and non-replicating persistent phenotype | Mycobacterium tuberculosis | |
0.01 | - |
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](p-tolyl)methanone | Kis value, mechanism is partial | Mycobacterium tuberculosis | |
0.01 | - |
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](p-tolyl)methanone | Kis value, mechanism is partial | Mycobacterium tuberculosis | |
0.014 | - |
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](m-tolyl)methanone | Ki value, mechanism is partial | Mycobacterium tuberculosis | |
0.016 | - |
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](p-tolyl)methanone | Ki value, mechanism is partial | Mycobacterium tuberculosis | |
0.016 | - |
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](o-tolyl)methanone | Kis value, mechanism is partial | Mycobacterium tuberculosis | |
0.02 | - |
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](m-tolyl)methanone | partial mechanism, Kis value | Escherichia coli | |
0.023 | - |
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](p-tolyl)methanone | Ki value, mechanism is partial | Mycobacterium tuberculosis | |
0.031 | - |
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](o-tolyl)methanone | partial mechanism, Ki value | Escherichia coli | |
0.036 | - |
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](o-tolyl)methanone | partial mechanism, Kis value | Escherichia coli | |
0.0366 | - |
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](m-tolyl)methanone | noncompetitive mechanism, the most potent antibiotic compound displays a minimum inhibitory concentration of 0.0366 mM versus Mycobacterium tuberculosis replicating phenotype, the compound and its analogues provide the first examples of riboflavin synthase inhibitors with antibiotic activity | Mycobacterium tuberculosis | |
0.038 | - |
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](m-tolyl)methanone | Kis value, mechanism is partial | Mycobacterium tuberculosis | |
0.0489 | - |
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](m-tolyl)methanone | noncompetitive mechanism, the most potent antibiotic compound displays a minimum inhibitory concentration of 0.0489 mM versus Mycobacterium tuberculosis nonreplicating phenotype | Mycobacterium tuberculosis | |
0.05 | - |
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](m-tolyl)methanone | partial mechanism, Ki value | Escherichia coli | |
0.057 | - |
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](o-tolyl)methanone | Kis value, mechanism is partial | Escherichia coli | |
0.061 | - |
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](p-tolyl)methanone | Ki value, mechanism is partial | Escherichia coli | |
0.091 | - |
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](m-tolyl)methanone | Kis value, mechanism is partial | Escherichia coli | |
0.104 | - |
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](p-tolyl)methanone | Kis value, mechanism is partial | Escherichia coli | |
0.106 | - |
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](m-tolyl)methanone | Ki value, mechanism is partial | Escherichia coli | |
0.135 | - |
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](p-tolyl)methanone | Ki value, mechanism is competitive | Escherichia coli | |
0.312 | - |
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](o-tolyl)methanone | Ki value, mechanism is partial | Escherichia coli |
General Information | Comment | Organism |
---|---|---|
physiological function | the product of the enzyme, riboflavin (also known as vitamin B2) is the central component of the cofactors FAD and FMN, enzyme plays a key role in energy production, and is required for the metabolism of fats, carbohydrates, and proteins | Mycobacterium tuberculosis |
physiological function | the product of the enzyme, riboflavin (also known as vitamin B2) is the central component of the cofactors FAD and FMN, enzyme plays a key role in energy production, and is required for the metabolism of fats, carbohydrates, and proteins | Escherichia coli |