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Literature summary extracted from

  • Cushman, M.; Sambaiah, T.; Jin, G.; Illarionov, B.; Fischer, M.; Bacher, A.
    Design, synthesis, and evaluation of 9-D-ribitylamino-1,3,7,9-tetrahydro-2,6,8-purinetriones bearing alkyl phosphate and alpha,alpha-difluorophosphonate substituents as inhibitors of riboflavin synthase and lumazine synthase (2004), J. Org. Chem., 69, 601-612.
    View publication on PubMed

Application

EC Number Application Comment Organism
2.5.1.78 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

EC Number Inhibitors Comment Organism Structure
2.5.1.78 1-deoxy-1-(2,6,8-trioxo-1,2,3,6,7,8-hexahydro-9H-purin-9-yl)-D-ribitol
-
Bacillus subtilis
2.5.1.78 1-deoxy-1-(2,6,8-trioxo-1,2,3,6,7,8-hexahydro-9H-purin-9-yl)-D-ribitol
-
Mycobacterium tuberculosis
2.5.1.78 1-deoxy-1-[(2,6-dioxo-5-[[5-(phosphonooxy)pentanoyl]amino]-1,2,3,6-tetrahydropyrimidin-4-yl)amino]-D-ribitol
-
Bacillus subtilis
2.5.1.78 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
2.5.1.78 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
2.5.1.78 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
2.5.1.78 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
2.5.1.78 1-deoxy-1-[[2,6-dioxo-5-(4-phosphonobutyl)-1,2,3,6-tetrahydropyrimidin-4-yl]amino]-D-ribitol
-
Bacillus subtilis
2.5.1.78 1-deoxy-1-[[2,6-dioxo-5-(5-phosphonopentyl)-1,2,3,6-tetrahydropyrimidin-4-yl]amino]-D-ribitol
-
Bacillus subtilis
2.5.1.78 1-deoxy-1-[[2,6-dioxo-5-(6-phosphonohexyl)-1,2,3,6-tetrahydropyrimidin-4-yl]amino]-D-ribitol
-
Bacillus subtilis
2.5.1.78 3-(1,3,7,9-tetrahydro-9-D-ribityl-2,6,8-trioxopurin-7-yl)-1-propanol
-
Mycobacterium tuberculosis
2.5.1.78 3-(1,3,7,9-tetrahydro-9-D-ribityl-2,6,8-trioxopurin-7-yl)propane 1-phosphate
-
Bacillus subtilis
2.5.1.78 3-(1,3,7,9-tetrahydro-9-D-ribityl-2,6,8-trioxopurin-7-yl)propane 1-phosphate
-
Mycobacterium tuberculosis
2.5.1.78 4-(1,3,7,9-tetrahydro-9-D-ribityl-2,6,8-trioxopurin-7-yl)butane 1-phosphate
-
Bacillus subtilis
2.5.1.78 4-(1,3,7,9-tetrahydro-9-D-ribityl-2,6,8-trioxopurin-7-yl)butane 1-phosphate
-
Mycobacterium tuberculosis
2.5.1.78 5-(1,3,7,9-tetrahydro-9-D-ribityl-2,6,8-trioxopurin-7-yl)-1,1-difluoropentane 1-phosphonate
-
Bacillus subtilis
2.5.1.78 5-(1,3,7,9-tetrahydro-9-D-ribityl-2,6,8-trioxopurin-7-yl)-1,1-difluoropentane 1-phosphonate
-
Mycobacterium tuberculosis
2.5.1.78 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]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.5.1.78 0.0052
-
L-3,4-dihydroxybutan-2-one 4-phosphate pH 7.0, 37°C, Tris buffer Bacillus subtilis
2.5.1.78 0.0052
-
L-3,4-dihydroxybutan-2-one 4-phosphate pH 7.0, 37°C, Tris buffer Mycobacterium tuberculosis
2.5.1.78 0.0067
-
L-3,4-dihydroxybutan-2-one 4-phosphate pH 7.0, 37°C, MOPS buffer Bacillus subtilis
2.5.1.78 0.0067
-
L-3,4-dihydroxybutan-2-one 4-phosphate pH 7.0, 37°C, MOPS buffer Mycobacterium tuberculosis
2.5.1.78 0.05
-
L-3,4-dihydroxybutan-2-one 4-phosphate pH 7.0, 37°C, phosphate buffer Bacillus subtilis
2.5.1.78 0.05
-
L-3,4-dihydroxybutan-2-one 4-phosphate pH 7.0, 37°C, phosphate buffer Mycobacterium tuberculosis

Organism

EC Number Organism UniProt Comment Textmining
2.5.1.78 Bacillus subtilis
-
-
-
2.5.1.78 Mycobacterium tuberculosis
-
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.5.1.78 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
-
?
2.5.1.78 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
-
?
2.5.1.78 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]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.5.1.78 37
-
assay at Bacillus subtilis

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.5.1.78 7
-
assay at Bacillus subtilis

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
2.5.1.78 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
2.5.1.78 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
2.5.1.78 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
2.5.1.78 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
2.5.1.78 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
2.5.1.78 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
2.5.1.78 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
2.5.1.78 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
2.5.1.78 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
2.5.1.78 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
2.5.1.78 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
2.5.1.78 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
2.5.1.78 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
2.5.1.78 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
2.5.1.78 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
2.5.1.78 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
2.5.1.78 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
2.5.1.78 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
2.5.1.78 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