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Information on EC 2.5.1.78 - 6,7-dimethyl-8-ribityllumazine synthase and Organism(s) Schizosaccharomyces pombe and UniProt Accession Q9UUB1

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IUBMB Comments
Involved in riboflavin biosynthesis.
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This record set is specific for:
Schizosaccharomyces pombe
UNIPROT: Q9UUB1
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Word Map
The taxonomic range for the selected organisms is: Schizosaccharomyces pombe
The enzyme appears in selected viruses and cellular organisms
Synonyms
lumazine synthase, 6,7-dimethyl-8-ribityllumazine synthase, ribh2, ribh1, mj0303, ribh1 protein, dmrl synthase, 6,7-dimethyl-8-(d-ribityl)lumazine synthase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6,7-dimethyl-8-ribityllumazine synthase
-
-
SYSTEMATIC NAME
IUBMB Comments
5-amino-6-(D-ribitylamino)uracil butanedionetransferase
Involved in riboflavin biosynthesis.
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
5-amino-6-(1-D-ribitylamino)pyrimidine-2,4(1H,3H)-dione + (S)-2-hydroxy-3-oxobutyl dihydrogen phosphate
6,7-dimethyl-8-(1-D-ribityl)lumazine + phosphate + 2 H2O
show the reaction diagram
5-amino-6-(1-D-ribitylamino)pyrimidine-2,4(1H,3H)-dione + (S)-2-hydroxy-3-oxobutyl dihydrogen phosphate
6,7-dimethyl-8-(1-D-ribityl)lumazine + phosphate + 2 H2O
show the reaction diagram
-
-
-
-
?
5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione + L-3,4-dihydroxybutan-2-one 4-phosphate
6,7-dimethyl-8-(1-D-ribityl)lumazine + 2 H2O + phosphate
show the reaction diagram
-
-
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
5-amino-6-(1-D-ribitylamino)pyrimidine-2,4(1H,3H)-dione + (S)-2-hydroxy-3-oxobutyl dihydrogen phosphate
6,7-dimethyl-8-(1-D-ribityl)lumazine + phosphate + 2 H2O
show the reaction diagram
5-amino-6-(1-D-ribitylamino)pyrimidine-2,4(1H,3H)-dione + (S)-2-hydroxy-3-oxobutyl dihydrogen phosphate
6,7-dimethyl-8-(1-D-ribityl)lumazine + phosphate + 2 H2O
show the reaction diagram
-
-
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ethyl [(2,4-dioxo-6-[[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino]-1,2,3,4-tetrahydropyrimidin-5-yl)amino](oxo)acetate
mixed type inhibition
(E)-3-hydroxy-4-(2-(5-nitro-2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-yl)vinyl)benzoic acid
-
-
(E)-4-(2-(5-nitro-2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-yl)vinyl)benzoate
-
-
(E)-5-nitro-6-(2-hydroxystyryl)pyrimidine-2,4(1H,3H)-dione
-
competitive
(E)-5-nitro-6-(3-nitrostyryl)pyrimidine-2,4(1H,3H)-dione
-
-
(E)-5-nitro-6-(4-nitrostyryl)pyrimidine-2,4(1H,3H)-dione
-
-
(E)-5-nitro-6-[2-(1H-pyrrol-2-yl)vinyl]pyrimidine-2,4(1H,3H)-dione
-
-
(E)-6-(2,3-dihydroxystyryl)-5-nitropyrimidine-2,4(1H,3H)-dione
-
-
(E)-6-(2,3-dimethoxystyryl)-5-nitropyrimidine-2,4(1H,3H)-dione
-
-
(E)-6-(2-(3H-indol-3-yl)vinyl)-5-nitropyrimidine-2,4(1H,3H)-dione
-
-
(E)-6-(2-(naphthalen-2-yl)vinyl)-5-nitropyrimidine-2,4(1H,3H)-dione
-
-
(E)-6-(2-fluoro-3-methoxystyryl)-5-nitropyrimidine-2,4(1H,3H)-dione
-
-
(E)-6-(2-methoxy-5-nitrostyryl)-5-nitropyrimidine-2,4(1H,3H)-dione
-
-
(E)-6-(2-methoxystyryl)-5-nitropyrimidine-2,4(1H,3H)-dione
-
-
(E)-6-(3-hydroxy-4-nitrostyryl)-5-nitropyrimidine-2,4(1H,3H)-dione
-
-
1,3,6,8-tetrahydroxynaphthyridine
-
-
2,4-dioxo-6-[[(2R,3R,4R)-2,3,4,5-tetrahydroxypentyl]sulfanyl]-1,2,3,4-tetrahydropyrimidin-5-aminium chloride
-
inhibition of both lumazine synthase and riboflavin synthase
2,5,8,11-tetraaza-5,11-dihydro-4,10-dihydroxyperylene-1,3,6,7,9,12-hexaone
-
-
5-nitro-6-(D-ribitylamino)-2,4(1H,3H)-pyrimidinedione
-
-
5-nitro-6-styryluracil
-
-
5-nitro-6-[[(2R,3R,4R)-2,3,4,5 tetrahydroxypentyl]sulfanyl]pyrimidine-2,4(1H,3H)-dione
-
inhibition of both lumazine synthase and riboflavin synthase
5-nitroso-6-(D-ribitylamino)-2,4(1H,3H)-pyrimidinedione
-
-
6-carboxyethyl-7-oxo-8-ribityllumazine
-
-
N-6-(ribitylamino)pyrimidine-2,4(1H,3H)-dion-5-ylpropionamide
-
competitive, inhibition of both lumazine synthase and riboflavin synthase
N-6-(ribitylamino)pyrimidine-2,4(1H,3H)-dione-5-ylisobutyramide
-
competitive, inhibition of both lumazine synthase and riboflavin synthase
N-[2,4-dioxo-6-(ribitylamino)-1,2,3,4-tetrahydropyrimidin-5-yl]oxalamic acid ethyl ester
-
mixed type inhibition, inhibition of both lumazine synthase and riboflavin synthase
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.003 - 0.46
5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione
0.065 - 0.187
L-3,4-dihydroxybutan-2-one 4-phosphate
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0011
ethyl [(2,4-dioxo-6-[[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino]-1,2,3,4-tetrahydropyrimidin-5-yl)amino](oxo)acetate
pH 7.0, 27°C
0.017
riboflavin
pH 7.0, 37°C, wild-type enzyme
0.13
(E)-3-hydroxy-4-(2-(5-nitro-2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-yl)vinyl)benzoic acid
-
pH 7.0, 27°C
0.041
(E)-4-(2-(5-nitro-2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-yl)vinyl)benzoate
-
pH 7.0, 27°C
0.21
(E)-5-nitro-6-(2-hydroxystyryl)pyrimidine-2,4(1H,3H)-dione
-
pH 7.0, 27°C
0.011
(E)-5-nitro-6-(3-nitrostyryl)pyrimidine-2,4(1H,3H)-dione
-
pH 7.0, 27°C
0.013
(E)-5-nitro-6-(4-nitrostyryl)pyrimidine-2,4(1H,3H)-dione
-
pH 7.0, 27°C
0.013
(E)-5-nitro-6-[2-(1H-pyrrol-2-yl)vinyl]pyrimidine-2,4(1H,3H)-dione
-
pH 7.0, 27°C
0.0049
(E)-6-(2,3-dihydroxystyryl)-5-nitropyrimidine-2,4(1H,3H)-dione
-
pH 7.0, 27°C
0.243
(E)-6-(2,3-dimethoxystyryl)-5-nitropyrimidine-2,4(1H,3H)-dione
-
pH 7.0, 27°C
0.141
(E)-6-(2-(3H-indol-3-yl)vinyl)-5-nitropyrimidine-2,4(1H,3H)-dione
-
pH 7.0, 27°C
0.094
(E)-6-(2-(naphthalen-2-yl)vinyl)-5-nitropyrimidine-2,4(1H,3H)-dione
-
pH 7.0, 27°C
0.151
(E)-6-(2-fluoro-3-methoxystyryl)-5-nitropyrimidine-2,4(1H,3H)-dione
-
pH 7.0, 27°C
0.085
(E)-6-(2-methoxy-5-nitrostyryl)-5-nitropyrimidine-2,4(1H,3H)-dione
-
pH 7.0, 27°C
0.205
(E)-6-(2-methoxystyryl)-5-nitropyrimidine-2,4(1H,3H)-dione
-
pH 7.0, 27°C
0.094
(E)-6-(3-hydroxy-4-nitrostyryl)-5-nitropyrimidine-2,4(1H,3H)-dione
-
pH 7.0, 27°C
0.35
1,3,6,8-tetrahydroxynaphthyridine
-
pH 7.0, 37°C
0.00016
2,4-dioxo-6-[[(2R,3R,4R)-2,3,4,5-tetrahydroxypentyl]sulfanyl]-1,2,3,4-tetrahydropyrimidin-5-aminium chloride
-
pH 7.0, 27°C
0.022 - 0.066
2,5,8,11-tetraaza-5,11-dihydro-4,10-dihydroxyperylene-1,3,6,7,9,12-hexaone
0.143
5-nitro-6-styryluracil
-
pH 7.0, 27°C
0.002
5-nitro-6-[[(2R,3R,4R)-2,3,4,5 tetrahydroxypentyl]sulfanyl]pyrimidine-2,4(1H,3H)-dione
-
pH 7.0, 27°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.011
N-6-(ribitylamino)pyrimidine-2,4(1H,3H)-dion-5-ylpropionamide
Schizosaccharomyces pombe
-
pH 7.0, 27°C
0.0079
N-6-(ribitylamino)pyrimidine-2,4(1H,3H)-dione-5-ylisobutyramide
Schizosaccharomyces pombe
-
pH 7.0, 27°C
0.00101
N-[2,4-dioxo-6-(ribitylamino)-1,2,3,4-tetrahydropyrimidin-5-yl]oxalamic acid ethyl ester
Schizosaccharomyces pombe
-
pH 7.0, 27°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
17188
5 * 17188, calculated from sequence
17189
5 * 17189, electrospray MS
87000
sedimentation equilibrium centrifugation
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pentamer
additional information
lumazine synthase is found in different species in two different quaternary structures, pentameric and icosahedral, built from practically the same structural monomeric unit. The icosahedral structure is best described as a capsid of twelve pentamers. Despite this noticeable difference, the active sites are virtually identical in all structurally studied members. The main regions involved in the catalysis are located at the interface between adjacent subunits in the pentamer. Combined analysis that includes sequence-structure and evolutionary studies to find the sequence determinants of the different quaternary assemblies of this enzyme. The positions involved in icosahedral contacts suffer a larger increase in constraints than the rest. Eight sequence sites that would be the most important icosahedral sequence determinants are identified
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
sitting-drop vapour diffusion method, crystallizes in space group C222(1). The crystals diffract to a resolution of 2.4 A
crystals are grown at 18°C by the sitting drop vapor diffusion method. The W27Y mutant protein in complex with riboflavin, the substrate analogue 5-nitroso-6-ribitylamino-2,4(1H,3H)-pyrimidinedione, and the product analogue 6-carboxyethyl-7-oxo-8-ribityllumazine, are determined by X-ray crystallography at resolutions of 2.7–2.8 A
-
sitting drop vapour diffusion method, the enzyme is crystallised either in complex with bound riboflavin (RIBO) or in complex with the substrate analogue 5-nitro-6-(D-ribitylamino)-2,4(1H,3H)-pyrimidinedione (NRAP) or the product analogue 6-carboxyethyl-7-oxo-8-ribityllumazine (CEOL). The mutant proteins W27G, W63Y and W63Y/L119F, which do not bind riboflavin, and the mutant L119F, which only weakly binds to riboflavin, are also analysed. Diffraction data are collected to resolutions of 2.4 A (RIBO), 2.4 A (NRAP), 2.6 A (CEOL), 2.0 A (W27G), 3.1 A (W63Y and L119F) and 2.7 A (W63Y/L119F), respectively. All crystals belong to space group C222(1) with one pentamer in the asymmetric unit corresponding to the solution state of the protein
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
W27F
the replacement of tryptophan 27 by aliphatic amino acids substantially reduces the affinity of the enzyme for riboflavin and for the substrate, 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione
W27G
the replacement of tryptophan 27 by aliphatic amino acids substantially reduces the affinity of the enzyme for riboflavin and for the substrate, 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione
W27H
the replacement of tryptophan 27 by aliphatic amino acids substantially reduces the affinity of the enzyme for riboflavin and for the substrate, 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione
W27I
the replacement of tryptophan 27 by aliphatic amino acids substantially reduces the affinity of the enzyme for riboflavin and for the substrate, 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione
W27S
the replacement of tryptophan 27 by aliphatic amino acids substantially reduces the affinity of the enzyme for riboflavin and for the substrate, 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione
W27Y
the replacement of tryptophan 27 by aliphatic amino acids substantially reduces the affinity of the enzyme for riboflavin and for the substrate, 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione
L119F
-
weakly binds to riboflavin
W27G
-
does not bind riboflavin
W27Y
-
whereas the indole system of W27 forms a coplanar pi-complex with riboflavin, the corresponding phenyl ring in the W27Y mutant establishes only peripheral contact with the heterocyclic ring system of the bound riboflavin
W63Y
-
does not bind riboflavin
W63Y/L119F
-
does not bind riboflavin
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Talukdar, A.; Illarionov, B.; Bacher, A.; Fischer, M.; Cushman, M.
Synthesis and enzyme inhibitory activity of the s-nucleoside analogue of the ribitylaminopyrimidine substrate of lumazine synthase and product of riboflavin synthase
J. Org. Chem.
72
7167-7175
2007
Bacillus subtilis, Mycobacterium tuberculosis, Schizosaccharomyces pombe
Manually annotated by BRENDA team
Zhang, Y.; Illarionov, B.; Morgunova, E.; Jin, G.; Bacher, A.; Fischer, M.; Ladenstein, R.; Cushman, M.
A new series of N-[2,4-dioxo-6-d-ribitylamino-1,2,3,4-tetrahydropyrimidin-5-yl]oxalamic acid derivatives as inhibitors of lumazine synthase and riboflavin synthase: design, synthesis, biochemical evaluation, crystallography, and mechanistic implications
J. Org. Chem.
73
2715-2724
2008
Bacillus subtilis, Mycobacterium tuberculosis, Schizosaccharomyces pombe
Manually annotated by BRENDA team
Fischer, M.; Haase, I.; Feicht, R.; Richter, G.; Gerhardt, S.; Changeux, J.P.; Huber, R.; Bacher A.
Biosynthesis of riboflavin: 6,7-dimethyl-8-ribityllumazine synthase of Schizosaccharomyces pombe
Eur. J. Biochem.
269
519-526
2002
Schizosaccharomyces pombe (Q9UUB1), Schizosaccharomyces pombe
Manually annotated by BRENDA team
Koch, M.; Breithaupt, C.; Gerhardt, S.; Haase, I.; Weber, S.; Cushman, M.; Huber, R.; Bacher, A.; Fischer, M.
Structural basis of charge transfer complex formation by riboflavin bound to 6,7-dimethyl-8-ribityllumazine synthase
Eur. J. Biochem.
271
3208-3214
2004
Schizosaccharomyces pombe
Manually annotated by BRENDA team
Gerhardt, S.; Haase, I.; Steinbacher, S.; Kaiser, J.T.; Cushman, M.; Bacher, A.; Huber, R.; Fischer, M.
The structural basis of riboflavin binding to Schizosaccharomyces pombe 6,7-dimethyl-8-ribityllumazine synthase
J. Mol. Biol.
318
1317-1329
2002
Schizosaccharomyces pombe
Manually annotated by BRENDA team
Zhang, Y.; Illarionov, B.; Bacher, A.; Fischer, M.; Georg, G.I.; Ye, Q.Z.; Vander Velde, D.; Fanwick, P.E.; Song, Y.; Cushman, M.
A novel lumazine synthase inhibitor derived from oxidation of 1,3,6,8-tetrahydroxy-2,7-naphthyridine to a tetraazaperylenehexaone derivative
J. Org. Chem.
72
2769-2776
2007
Schizosaccharomyces pombe
Manually annotated by BRENDA team
Talukdar, A.; Breen, M.; Bacher, A.; Illarionov, B.; Fischer, M.; Georg, G.; Ye, Q.Z.; Cushman, M.
Discovery and development of a small molecule library with lumazine synthase inhibitory activity
J. Org. Chem.
74
5123-5134
2009
Mycobacterium tuberculosis, Schizosaccharomyces pombe
Manually annotated by BRENDA team
Fornasari, M.S.; Laplagne, D.A.; Frankel, N.; Cauerhff, A.A.; Goldbaum, F.A.; Echave, J.
Sequence determinants of quaternary structure in lumazine synthase
Mol. Biol. Evol.
21
97-107
2003
Spinacia oleracea, Corynebacterium ammoniagenes (O24753), Helicobacter pylori (O24854), Methanothermobacter thermautotrophicus (O27443), Archaeoglobus fulgidus (O28152), Aquifex aeolicus (O66529), Sulfurospirillum multivorans (O68250), Arabidopsis thaliana (O80575), Chlamydia trachomatis (O84737), Bacillus subtilis (P11998), Haemophilus influenzae (P45149), Actinobacillus pleuropneumoniae (P50856), Saccharomyces cerevisiae (P50861), Photobacterium phosphoreum (P51963), Pasteurella multocida (P57869), Brucella abortus (P61711), Synechocystis sp. (P73527), Photobacterium leiognathi (Q01994), Photobacterium leiognathi (Q93E92), Bacillus amyloliquefaciens (Q44681), Rhodococcus erythropolis (Q53107), Methanocaldococcus jannaschii (Q57751), Buchnera aphidicola (Q8K9A6), Buchnera aphidicola (Q9ZNM0), Chlorobaculum tepidum (Q8KAW4), Corynebacterium glutamicum (Q8NQ53), Xanthomonas campestris (Q8PCM7), Xanthomonas citri (Q8PPD6), Methanosarcina mazei (Q8Q093), Fusobacterium nucleatum (Q8RIR4), Methanosarcina acetivorans (Q8TPT7), Methanopyrus kandleri (Q8TYL5), Agrobacterium tumefaciens (Q8UG70), Clostridium perfringens (Q8XMW9), Ralstonia solanacearum (Q8Y1H8), Anabaena sp. (Q8YQ43), Yersinia pestis (Q8ZC41), Pyrobaculum aerophilum (Q8ZTE3), Sinorhizobium meliloti (Q92NI1), Sinorhizobium meliloti (Q92QU0), Sulfurisphaera tokodaii (Q975M5), Clostridium acetobutylicum (Q97LG8), Mesorhizobium loti (Q983B0), Mesorhizobium loti (Q986N2), Caulobacter vibrioides (Q9A8J4), Caulobacter vibrioides (Q9A9S4), Mycobacterium leprae (Q9CCP3), Lactococcus lactis subsp. lactis (Q9CGU6), Streptomyces coelicolor (Q9EWJ9), Halobacterium salinarum (Q9HRM5), Pseudomonas aeruginosa (Q9HWX5), Halalkalibacterium halodurans (Q9KCL4), Vibrio cholerae (Q9KPU4), Xylella fastidiosa (Q9PES4), Campylobacter jejuni (Q9PIB9), Chlamydia muridarum (Q9PLJ4), Bartonella henselae (Q9REF4), Deinococcus radiodurans (Q9RXZ8), Schizosaccharomyces pombe (Q9UUB1), Pyricularia grisea (Q9UVT8), Thermotoga maritima (Q9X2E5), Nicotiana tabacum (Q9XH13), Chlamydia pneumoniae (Q9Z733), Helicobacter pylori J99 (Q9ZN56), Agrobacterium tumefaciens C58 / ATCC 33970 (Q8UG70)
Manually annotated by BRENDA team
Talukdar, A.; Zhao, Y.; Lv, W.; Bacher, A.; Illarionov, B.; Fischer, M.; Cushman, M.
O-Nucleoside, S-nucleoside, and N-nucleoside probes of lumazine synthase and riboflavin synthase
J. Org. Chem.
77
6239-6261
2012
Bacillus subtilis, Mycobacterium tuberculosis, Schizosaccharomyces pombe (Q9UUB1)
Manually annotated by BRENDA team