Application | Comment | Organism |
---|---|---|
medicine | certain purinetriones bearing phosphate side chains can inhibit both lumazine synthase as well as riboflavin synthase, and molecular modeling with 3-(1,3,7,9-tetrahydro-9-D-ribityl-2,6,8-trioxopurin-7-yl)propane 1-phosphate suggests possible binding modes to each enzyme. Antibiotics that would inhibit both lumazine synthase and riboflavin synthase would be less likely to suffer from the development of antibiotic resistance by the organisms that they are supposed to treat, since pathogenic microorganisms would have to simultaneously select for mutations in both enzymes in order to escape the cytotoxic effects of the antibiotics | Bacillus subtilis |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
1-deoxy-1-(2,6,8-trioxo-1,2,3,6,7,8-hexahydro-9H-purin-9-yl)-D-ribitol | - |
Bacillus subtilis | |
1-deoxy-1-(2,6,8-trioxo-1,2,3,6,7,8-hexahydro-9H-purin-9-yl)-D-ribitol | - |
Mycobacterium tuberculosis | |
1-deoxy-1-[(2,6-dioxo-5-[[5-(phosphonooxy)pentanoyl]amino]-1,2,3,6-tetrahydropyrimidin-4-yl)amino]-D-ribitol | - |
Bacillus subtilis | |
1-deoxy-1-[2,6,8-trioxo-7-[5-(phosphonooxy)pentyl]-1,2,3,6,7,8-hexahydro-9H-purin-9-yl]-D-ribitol | - |
Bacillus subtilis | |
1-deoxy-1-[2,6,8-trioxo-7-[5-(phosphonooxy)pentyl]-1,2,3,6,7,8-hexahydro-9H-purin-9-yl]-D-ribitol | - |
Mycobacterium tuberculosis | |
1-deoxy-1-[2,6,8-trioxo-7-[6-(phosphonooxy)hexyl]-1,2,3,6,7,8-hexahydro-9H-purin-9-yl]-D-ribitol | - |
Bacillus subtilis | |
1-deoxy-1-[2,6,8-trioxo-7-[6-(phosphonooxy)hexyl]-1,2,3,6,7,8-hexahydro-9H-purin-9-yl]-D-ribitol | - |
Mycobacterium tuberculosis | |
1-deoxy-1-[[2,6-dioxo-5-(4-phosphonobutyl)-1,2,3,6-tetrahydropyrimidin-4-yl]amino]-D-ribitol | - |
Bacillus subtilis | |
1-deoxy-1-[[2,6-dioxo-5-(5-phosphonopentyl)-1,2,3,6-tetrahydropyrimidin-4-yl]amino]-D-ribitol | - |
Bacillus subtilis | |
1-deoxy-1-[[2,6-dioxo-5-(6-phosphonohexyl)-1,2,3,6-tetrahydropyrimidin-4-yl]amino]-D-ribitol | - |
Bacillus subtilis | |
3-(1,3,7,9-tetrahydro-9-D-ribityl-2,6,8-trioxopurin-7-yl)-1-propanol | - |
Mycobacterium tuberculosis | |
3-(1,3,7,9-tetrahydro-9-D-ribityl-2,6,8-trioxopurin-7-yl)propane 1-phosphate | - |
Bacillus subtilis | |
3-(1,3,7,9-tetrahydro-9-D-ribityl-2,6,8-trioxopurin-7-yl)propane 1-phosphate | - |
Mycobacterium tuberculosis | |
4-(1,3,7,9-tetrahydro-9-D-ribityl-2,6,8-trioxopurin-7-yl)butane 1-phosphate | - |
Bacillus subtilis | |
4-(1,3,7,9-tetrahydro-9-D-ribityl-2,6,8-trioxopurin-7-yl)butane 1-phosphate | - |
Mycobacterium tuberculosis | |
5-(1,3,7,9-tetrahydro-9-D-ribityl-2,6,8-trioxopurin-7-yl)-1,1-difluoropentane 1-phosphonate | - |
Bacillus subtilis | |
5-(1,3,7,9-tetrahydro-9-D-ribityl-2,6,8-trioxopurin-7-yl)-1,1-difluoropentane 1-phosphonate | - |
Mycobacterium tuberculosis | |
additional information | certain purinetriones bearing phosphate side chains can inhibit both lumazine synthase as well as riboflavin synthase, and molecular modeling with 3-(1,3,7,9-tetrahydro-9-D-ribityl-2,6,8-trioxopurin-7-yl)propane 1-phosphate suggests possible binding modes to each enzyme. Antibiotics that would inhibit both lumazine synthase and riboflavin synthase would be less likely to suffer from the development of antibiotic resistance by the organisms that they are supposed to treat, since pathogenic microorganisms would have to simultaneously select for mutations in both enzymes in order to escape the cytotoxic effects of the antibiotics | Bacillus subtilis |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.0052 | - |
L-3,4-dihydroxybutan-2-one 4-phosphate | pH 7.0, 37°C, Tris buffer | Bacillus subtilis | |
0.0052 | - |
L-3,4-dihydroxybutan-2-one 4-phosphate | pH 7.0, 37°C, Tris buffer | Mycobacterium tuberculosis | |
0.0067 | - |
L-3,4-dihydroxybutan-2-one 4-phosphate | pH 7.0, 37°C, MOPS buffer | Bacillus subtilis | |
0.0067 | - |
L-3,4-dihydroxybutan-2-one 4-phosphate | pH 7.0, 37°C, MOPS buffer | Mycobacterium tuberculosis | |
0.05 | - |
L-3,4-dihydroxybutan-2-one 4-phosphate | pH 7.0, 37°C, phosphate buffer | Bacillus subtilis | |
0.05 | - |
L-3,4-dihydroxybutan-2-one 4-phosphate | pH 7.0, 37°C, phosphate buffer | Mycobacterium tuberculosis |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Bacillus subtilis | - |
- |
- |
Mycobacterium tuberculosis | - |
- |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
5-amino-6-(1-D-ribitylamino)pyrimidine-2,4(1H,3H)-dione + (3R)-3,4-dihydroxy-2-butanone 4-phosphate | - |
Bacillus subtilis | 6,7-dimethyl-8-(1-D-ribityl)lumazine + 2 H2O + phosphate | - |
? | |
5-amino-6-(1-D-ribitylamino)pyrimidine-2,4(1H,3H)-dione + (S)-2-hydroxy-3-oxobutyl dihydrogen phosphate | - |
Bacillus subtilis | 6,7-dimethyl-8-(1-D-ribityl)lumazine + phosphate + 2 H2O | - |
? | |
5-amino-6-(1-D-ribitylamino)pyrimidine-2,4(1H,3H)-dione + (S)-2-hydroxy-3-oxobutyl dihydrogen phosphate | - |
Mycobacterium tuberculosis | 6,7-dimethyl-8-(1-D-ribityl)lumazine + phosphate + 2 H2O | - |
? |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Bacillus subtilis |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7 | - |
assay at | Bacillus subtilis |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
0.0026 | - |
3-(1,3,7,9-tetrahydro-9-D-ribityl-2,6,8-trioxopurin-7-yl)-1-propanol | pH 7.0, 37°C, variable concentration of 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione | Mycobacterium tuberculosis | |
0.0041 | - |
4-(1,3,7,9-tetrahydro-9-D-ribityl-2,6,8-trioxopurin-7-yl)butane 1-phosphate | pH 7.0, 37°C, variable concentration of 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione | Mycobacterium tuberculosis | |
0.0045 | - |
3-(1,3,7,9-tetrahydro-9-D-ribityl-2,6,8-trioxopurin-7-yl)propane 1-phosphate | pH 7.0, 37°C, variable concentration of 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione | Mycobacterium tuberculosis | |
0.0047 | - |
1-deoxy-1-[2,6,8-trioxo-7-[5-(phosphonooxy)pentyl]-1,2,3,6,7,8-hexahydro-9H-purin-9-yl]-D-ribitol | pH 7.0, 37°C, variable concentration of 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione | Mycobacterium tuberculosis | |
0.0091 | - |
1-deoxy-1-(2,6,8-trioxo-1,2,3,6,7,8-hexahydro-9H-purin-9-yl)-D-ribitol | pH 7.0, 37°C, variable concentration of 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione | Mycobacterium tuberculosis | |
0.0414 | - |
3-(1,3,7,9-tetrahydro-9-D-ribityl-2,6,8-trioxopurin-7-yl)propane 1-phosphate | pH 7.0, 37°C, variable concentration of 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione | Bacillus subtilis | |
0.046 | - |
1-deoxy-1-(2,6,8-trioxo-1,2,3,6,7,8-hexahydro-9H-purin-9-yl)-D-ribitol | pH 7.0, 37°C, variable concentration of L-3,4-dihydroxybutan-2-one 4-phosphate | Bacillus subtilis | |
0.06 | - |
5-(1,3,7,9-tetrahydro-9-D-ribityl-2,6,8-trioxopurin-7-yl)-1,1-difluoropentane 1-phosphonate | pH 7.0, 37°C, variable concentration of 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione | Mycobacterium tuberculosis | |
0.0783 | - |
1-deoxy-1-[2,6,8-trioxo-7-[6-(phosphonooxy)hexyl]-1,2,3,6,7,8-hexahydro-9H-purin-9-yl]-D-ribitol | pH 7.0, 37°C, variable concentration of 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione | Bacillus subtilis | |
0.13 | - |
1-deoxy-1-[[2,6-dioxo-5-(6-phosphonohexyl)-1,2,3,6-tetrahydropyrimidin-4-yl]amino]-D-ribitol | pH 7.0, 37°C, variable concentration of L-3,4-dihydroxybutan-2-one 4-phosphate | Bacillus subtilis | |
0.132 | - |
5-(1,3,7,9-tetrahydro-9-D-ribityl-2,6,8-trioxopurin-7-yl)-1,1-difluoropentane 1-phosphonate | pH 7.0, 37°C, variable concentration of 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione | Bacillus subtilis | |
0.168 | - |
4-(1,3,7,9-tetrahydro-9-D-ribityl-2,6,8-trioxopurin-7-yl)butane 1-phosphate | pH 7.0, 37°C, variable concentration of 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione | Bacillus subtilis | |
0.17 | - |
1-deoxy-1-[2,6,8-trioxo-7-[6-(phosphonooxy)hexyl]-1,2,3,6,7,8-hexahydro-9H-purin-9-yl]-D-ribitol | pH 7.0, 37°C, variable concentration of 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione | Mycobacterium tuberculosis | |
0.175 | - |
1-deoxy-1-[2,6,8-trioxo-7-[6-(phosphonooxy)hexyl]-1,2,3,6,7,8-hexahydro-9H-purin-9-yl]-D-ribitol | pH 7.0, 37°C, variable concentration of L-3,4-dihydroxybutan-2-one 4-phosphate | Bacillus subtilis | |
0.18 | - |
1-deoxy-1-[[2,6-dioxo-5-(5-phosphonopentyl)-1,2,3,6-tetrahydropyrimidin-4-yl]amino]-D-ribitol | pH 7.0, 37°C, variable concentration of L-3,4-dihydroxybutan-2-one 4-phosphate | Bacillus subtilis | |
0.271 | - |
1-deoxy-1-[2,6,8-trioxo-7-[5-(phosphonooxy)pentyl]-1,2,3,6,7,8-hexahydro-9H-purin-9-yl]-D-ribitol | pH 7.0, 37°C, variable concentration of 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione | Bacillus subtilis | |
0.44 | - |
1-deoxy-1-[[2,6-dioxo-5-(4-phosphonobutyl)-1,2,3,6-tetrahydropyrimidin-4-yl]amino]-D-ribitol | pH 7.0, 37°C, variable concentration of L-3,4-dihydroxybutan-2-one 4-phosphate | Bacillus subtilis | |
0.83 | - |
1-deoxy-1-[(2,6-dioxo-5-[[5-(phosphonooxy)pentanoyl]amino]-1,2,3,6-tetrahydropyrimidin-4-yl)amino]-D-ribitol | pH 7.0, 37°C, variable concentration of L-3,4-dihydroxybutan-2-one 4-phosphate | Bacillus subtilis | |
0.852 | - |
1-deoxy-1-[2,6,8-trioxo-7-[5-(phosphonooxy)pentyl]-1,2,3,6,7,8-hexahydro-9H-purin-9-yl]-D-ribitol | pH 7.0, 37°C, variable concentration of L-3,4-dihydroxybutan-2-one 4-phosphate | Bacillus subtilis |