Any feedback?
Information on EC 2.5.1.9 - riboflavin synthase and Organism(s) Escherichia coli and UniProt Accession P0AFU8
for references in articles please use BRENDA:EC2.5.1.9Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
2.5.1.9 riboflavin synthaseIUBMB Comments
A flavoprotein (riboflavin).
Specify your search results
Word Map
- 2.5.1.9
- 6,7-dimethyl-8-ribityllumazine
-
cyclohydrolase
-
5-amino-6-ribitylamino-2,41h,3h-pyrimidinedione
-
dismutation
- guilliermondii
- 3,4-dihydroxy-2-butanone
-
icosahedral
-
bartonellae
- photobacterium
-
flavinogenic
-
flavinogenesis
-
ashbyii
- eremothecium
-
ribitylated
- leiognathi
- henselae
- famata
- drug development
- pharmacology
- medicine
The taxonomic range for the selected organisms is: Escherichia coli
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
Reaction Schemes
Synonyms
riboflavin synthase, riboflavin synthetase, heavy riboflavin synthase, light riboflavin synthase, lumazine synthase/riboflavin synthase complex, riboflavine synthetase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
light riboflavin synthase
-
-
-
-
riboflavin synthetase
-
-
-
-
riboflavine synthase
-
-
-
-
riboflavine synthetase
-
-
-
-
synthase, riboflavin
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
Cys-48 plays a nucleophilic role in catalytic mechanism
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
active site structure and catalytic mechanism
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
reaction mechanism
-
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
active site
-
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
substrate binding site
-
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
catalytic mechanism, stereochemistry, pentacyclic reaction intermediate which is diastereomeric to the reaction intermediate of the enzyme from Methanococcus jannaschii
-
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
detailed catalytic mechanism, pentacyclic reaction intermediate
-
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
pentacyclic reaction intermediate
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dismutation
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -, -
SYSTEMATIC NAME
IUBMB Comments
6,7-dimethyl-8-(1-D-ribityl)lumazine:6,7-dimethyl-8-(1-D-ribityl)lumazine 2,3-butanediyltransferase
A flavoprotein (riboflavin).
CAS REGISTRY NUMBER
COMMENTARY
9075-82-5
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
-
-
-
?
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
2 6,7-dimethyl-8-ribityllumazine
riboflavin + 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidine-dione
-
the reaction catalyzed by riboflavin synthase of Methanococcus jannaschii involves a pentacyclic intermediate, which is a diastereomer of the pentacyclic intermediate of riboflavin synthase of Escherichia coli
-
-
?
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
dismutation
riboflavin binding site structure
-
?
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
ultimate step in the biosynthesis of riboflavin, i.e. vitamin B2, the precursor of flavin cofactors
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
-
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
1 riboflavin is bound per monomer in a site at one end of the 6-stranded antiparallel beta-barrel which is comprised of elements of both monomers
-
-
?
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
-
-
-
-
?
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
-
enzyme catalyzes the transfer of a four-carbon unit between 2 molecules of the substrate, 6,7-dimethyl-8-ribityllumazine
-
-
?
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
-
-
-
-
r
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
-
final step of biosynthesis of vitamin B2, i.e. riboflavin, the universal precursor of flavocoenzymes, overview
-
-
?
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
-
dismutation, exchange of a C4 fragment, regio- and stereospecific reaction
-
-
?
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
-
mechanistical complex dismutation
-
-
r
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
-
mechanistically complex dismutation
-
-
r
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
-
-
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
-
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
-
-
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
-
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
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
-
-
?
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
-
-
?
additional information
?
-
-
no activity with the dimeric pentacyclic reaction intermediate as substrate
-
-
?
additional information
?
-
-
utilization of the pentacyclic reaction intermediate as substrate
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
-
-
-
?
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
ultimate step in the biosynthesis of riboflavin, i.e. vitamin B2, the precursor of flavin cofactors
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
-
-
-
?
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
-
enzyme catalyzes the transfer of a four-carbon unit between 2 molecules of the substrate, 6,7-dimethyl-8-ribityllumazine
-
-
?
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
-
-
-
-
?
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
-
-
-
-
r
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
-
final step of biosynthesis of vitamin B2, i.e. riboflavin, the universal precursor of flavocoenzymes, overview
-
-
?
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
-
-
?
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
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](m-tolyl)methanone
covalent hydrate of trifluoromethylated pyrazole
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](o-tolyl)methanone
covalent hydrate of trifluoromethylated pyrazole
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](p-tolyl)methanone
covalent hydrate of trifluoromethylated pyrazole
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](m-tolyl)methanone
covalent hydrate of trifluoromethylated pyrazole
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](o-tolyl)methanone
covalent hydrate of trifluoromethylated pyrazole
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](p-tolyl)methanone
covalent hydrate of trifluoromethylated pyrazole
1-deoxy-1-[2,6,8-trioxo-7-[4-(phosphonooxy)butyl]-1,2,3,6,7,8-hexahydro-9H-purin-9-yl]-D-ribitol
-
competitive inhibition
2,4-dioxo-6-[(3S,4S,5R)-3,4,5,6-tetrahydroxyhexyl]-1,2,3,4-tetrahydropyrimidin-5-aminium chloride
-
uncompetitive inhibition
2,4-dioxo-6-[[(2R,3R,4R)-2,3,4,5-tetrahydroxypentyl]sulfanyl]-1,2,3,4-tetrahydropyrimidin-5-aminium chloride
-
-
2-chloro-N-(2,4-dioxo-6-((2S,3S,4R)-2,3,4,5-tetrahydroxypentylamino)-1,2,3,4-tetrahydropyrimidin-5-yl)acetamide
-
-
2-chloro-N-(2,4-dioxo-6-((2S,3S,4R)-2,3,4,5-tetrahydroxypentylamino)-1,2,3,4-tetrahydropyrimidin-5-yl)propanamide
-
-
4-[2,4,7-trioxo-8-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]-1,2,3,4,7,8-hexahydropteridin-6-yl]butanoic acid
-
comparison with inhibition of Bacillus subtilis lumazine synthase
4-[2,4,7-trioxo-8-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]-1,2,3,4,7,8-hexahydropteridin-6-yl]butyl dihydrogen phosphate
-
comparison with inhibition of Bacillus subtilis lumazine synthase
4-[2,4,7-trioxo-8-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]-1,2,3,4,7,8-hexahydropteridin-6-yl]propyl dihydrogen phosphate
-
competitive, comparison with inhibition of Bacillus subtilis lumazine synthase
5-(4-phosphonobutyryl)amino-6-D-ribitylaminouracil
-
comparison with inhibition of Bacillus subtilis luminazine synthase/riboflavin synthase
5-(4-phosphonopentyryl)amino-6-D-ribitylaminouracil
-
comparison with inhibition of Bacillus subtilis luminazine synthase/riboflavin synthase
5-(5-phosphonoxyvaleryl)amino-6-D-ribitylaminouracil
-
mixed inhibition, comparison with inhibition of Bacillus subtilis luminazine synthase/riboflavin synthase
5-(hexyl 6-dihydrogen phosphate)-6-([(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino)pyrimidine-2,4(1H,3H)-dione
5-(pentyl 6-dihydrogen phosphate)-6-([(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino)pyrimidine-2,4(1H,3H)-dione
-
comparison with inhibition of Bacillus subtilis lumazine synthase
5-amino-6-((2R,3R,4S)-2,3,4,5-tetrahydroxypentyloxy)-pyrimidine-2,4(1H,3H)-dione
-
uncompetitive inhibition
5-amino-6-[[(2R,3R,4R)-2,3,4,5-tetrahydroxypentyl]sulfanyl]pyrimidine-2,4(1H,3H)-dione
-
partial inhibition
5-nitro-6-[(3S,4S,5R)-3,4,5,6-tetrahydroxyhexyl]pyrimidine-2,4(1H,3H)-dione
-
partial inhibition
5-nitro-6-[[(2R,3R,4R)-2,3,4,5 tetrahydroxypentyl]sulfanyl]pyrimidine-2,4(1H,3H)-dione
-
-
5-nitro-6-[[(2R,3R,4R)-2,3,4,5-tetrahydroxypentyl]sulfanyl]pyrimidine-2,4(1H,3H)-dione
-
partial inhibition
5-nitro-6-[[(2S,3R,4R)-2,3,4,5-tetrahydroxypentyl]oxy]pyrimidine-2,4(1H,3H)-dione
-
competitive inhibition
5-nitro-6-[[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino]pyrimidine-2,4(1H,3H)-dione
-
mixed-type inhibition
6-methyl-7-methylidene-8-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]-7,8-dihydropyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione
-
competitive, comparison with inhibition of Bacillus subtilis lumazine synthase
7-hydroxy-7-methyl-8-((2S,3S,4R)-2,3,4,5-tetrahydroxypentyl)-7,8-dihydropteridin-2,4,6(1H,3H,5H)-trione
-
-
8-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]-5,8-dihydropteridine-2,4,6,7(1H,3H)-tetrone
-
competitive inhibition
ethyl 2-(2,4-dioxo-6-((2S,3R,4R)-2,3,4,5-tetrahydroxypentyloxy)-1,2,3,4-tetrahydropyrimidin-5-ylamino)-2-oxoacetate
-
uncompetitive inhibition
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
ethyl [(6-chloro-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)amino](oxo)acetate
-
-
methyl 2-(2,4-dioxo-6-((2S,3R,4R)-2,3,4,5-tetrahydroxypentyloxy)-1,2,3,4-tetrahydropyrimidin-5-ylamino)-2-oxoacetate
-
uncompetitive inhibition
N-(2,4-dioxo-6-((2R,3R,4R)-2,3,4,5-tetrahydroxypentylthio)-1,2,3,4-tetrahydropyrimidin-5-yl)methacrylamide
-
-
N-(2,4-dioxo-6-((2R,3R,4R)-2,3,4,5-tetrahydroxypentylthio)-1,2,3,4-tetrahydropyrimidin-5-yl)propionamide
-
-
N-(2,4-dioxo-6-((2S,3R,4R)-2,3,4,5-tetrahydroxypentyloxy)-1,2,3,4-tetrahydropyrimidin-5-yl)isobutyramide
-
-
N-(2,4-dioxo-6-((2S,3R,4R)-2,3,4,5-tetrahydroxypentyloxy)-1,2,3,4-tetrahydropyrimidin-5-yl)methacrylamide
-
-
N-(2,4-dioxo-6-((2S,3R,4R)-2,3,4,5-tetrahydroxypentyloxy)-1,2,3,4-tetrahydropyrimidin-5-yl)propionamide
-
-
N-(2,4-dioxo-6-((2S,3S,4R)-2,3,4,5-tetrahydroxypentylamino)-1,2,3,4-tetrahydropyrimidin-5-yl)-3,3,3-trifluoropropanamide
-
-
N-(2,4-dioxo-6-[[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino]-1,2,3,4-tetrahydropyrimidin-5-yl)-2-methylpropanamide
-
uncompetitive inhibition
N-(2,4-dioxo-6-[[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino]-1,2,3,4-tetrahydropyrimidin-5-yl)propanamide
-
uncompetitive inhibition
N-6-(ribitylamino)pyrimidine-2,4(1H,3H)-dion-5-ylpropionamide
-
uncompetitive
N-6-(ribitylamino)pyrimidine-2,4(1H,3H)-dione-5-ylisobutyramide
-
uncompetitive
N-[2,4-dioxo-6-((2S,3S,4R)-2,3,4,5-tetrahydroxypentylamino]-1,2,3,4-tetrahydropyrimidin-5-yl)methacrylamide
-
-
N-[2,4-dioxo-6-(ribitylamino)-1,2,3,4-tetrahydropyrimidin-5-yl]oxalamic acid ethyl ester
-
mixed type inhibition
additional information
-
incorporation of an amide into 5-phosphonoalkyl-6-D-ribitylaminopyrimidinedione lumazine synthase inhibitors results in an unexpected reversal of selectivity for riboflavin synthase versus lumazine synthase
-
5-(hexyl 6-dihydrogen phosphate)-6-([(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino)pyrimidine-2,4(1H,3H)-dione
-
comparison with inhibition of Bacillus subtilis lumazine synthase
5-(hexyl 6-dihydrogen phosphate)-6-([(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino)pyrimidine-2,4(1H,3H)-dione
-
mixed inhibition, comparison with inhibition of Bacillus subtilis luminazine synthase/riboflavin synthase
9-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]-7,9-dihydro-1H-purine-2,6,8(3H)-trione
-
competitive inhibition
9-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]-7,9-dihydro-1H-purine-2,6,8(3H)-trione
-
competitive, comparison with inhibition of Bacillus subtilis lumazine synthase
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
presteady state kinetic analysis, single turnover conditions, transient stopped flow and quenched flow kinetics measurements of the pentacyclic reaction intermediate
-
additional information
additional information
-
steady-state and presteady-state kinetic analysis, single turnover conditions, transient stopped flow and quenched flow kinetics measurements with the pentacyclic reaction intermediate as substrate
-
additional information
additional information
-
stopped flow and quenched flow kinetics of wild-type enzyme and mutant S41A
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.001
6,7-dimethyl-8-(1-D-ribityl)lumazine
-
pH 6.9, 25°C, recombinant mutant H102Q, steady-state conditions
0.267
6,7-dimethyl-8-(1-D-ribityl)lumazine
-
pH 6.9, 25°C, recombinant wild-type enzyme, steady-state conditions
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.091 - 0.106
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](m-tolyl)methanone
0.031 - 0.036
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](o-tolyl)methanone
0.135
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](p-tolyl)methanone
Ki value, mechanism is competitive
0.02 - 0.05
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](m-tolyl)methanone
0.057 - 0.312
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](o-tolyl)methanone
0.061 - 0.104
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](p-tolyl)methanone
0.332
1-deoxy-1-[2,6,8-trioxo-7-[4-(phosphonooxy)butyl]-1,2,3,6,7,8-hexahydro-9H-purin-9-yl]-D-ribitol
-
in 100 mM Tris-HCl, pH 7.0, 100 mM NaCl, 2% (v/v) DMSO, 5 mM dithiothreitol, at 27°C
0.047
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
0.02
4-[2,4,7-trioxo-8-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]-1,2,3,4,7,8-hexahydropteridin-6-yl]butanoic acid
-
pH 7.5, 37°C
0.15
4-[2,4,7-trioxo-8-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]-1,2,3,4,7,8-hexahydropteridin-6-yl]butyl dihydrogen phosphate
-
pH 7.5, 37°C
1.6
4-[2,4,7-trioxo-8-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]-1,2,3,4,7,8-hexahydropteridin-6-yl]propyl dihydrogen phosphate
-
pH 7.5, 37°C
1
5-(hexyl 6-dihydrogen phosphate)-6-([(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino)pyrimidine-2,4(1H,3H)-dione
-
pH 7.5, 37°C
1
5-(pentyl 6-dihydrogen phosphate)-6-([(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino)pyrimidine-2,4(1H,3H)-dione
-
pH 7.5, 37°C
0.047
5-amino-6-[[(2R,3R,4R)-2,3,4,5-tetrahydroxypentyl]sulfanyl]pyrimidine-2,4(1H,3H)-dione
-
in 100 mM Tris-HCl, pH 7.0, 100 mM NaCl, 2% (v/v) DMSO, 5 mM dithiothreitol, at 27°C
0.037
5-nitro-6-[(3S,4S,5R)-3,4,5,6-tetrahydroxyhexyl]pyrimidine-2,4(1H,3H)-dione
-
in 100 mM Tris-HCl, pH 7.0, 100 mM NaCl, 2% (v/v) DMSO, 5 mM dithiothreitol, at 27°C
0.0027
5-nitro-6-[[(2R,3R,4R)-2,3,4,5 tetrahydroxypentyl]sulfanyl]pyrimidine-2,4(1H,3H)-dione
-
pH 7.0, 27°C
0.0027
5-nitro-6-[[(2R,3R,4R)-2,3,4,5-tetrahydroxypentyl]sulfanyl]pyrimidine-2,4(1H,3H)-dione
-
in 100 mM Tris-HCl, pH 7.0, 100 mM NaCl, 2% (v/v) DMSO, 5 mM dithiothreitol, at 27°C
0.038
5-nitro-6-[[(2S,3R,4R)-2,3,4,5-tetrahydroxypentyl]oxy]pyrimidine-2,4(1H,3H)-dione
-
in 100 mM Tris-HCl, pH 7.0, 100 mM NaCl, 2% (v/v) DMSO, 5 mM dithiothreitol, at 27°C
0.008
5-nitro-6-[[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino]pyrimidine-2,4(1H,3H)-dione
-
in 100 mM Tris-HCl, pH 7.0, 100 mM NaCl, 2% (v/v) DMSO, 5 mM dithiothreitol, at 27°C
0.65
6-methyl-7-methylidene-8-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]-7,8-dihydropyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione
-
pH 7.5, 37°C
0.0000062
8-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]-5,8-dihydropteridine-2,4,6,7(1H,3H)-tetrone
-
in 100 mM Tris-HCl, pH 7.0, 100 mM NaCl, 2% (v/v) DMSO, 5 mM dithiothreitol, at 27°C
0.0000013
ethyl [(2,4-dioxo-6-[[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino]-1,2,3,4-tetrahydropyrimidin-5-yl)amino](oxo)acetate
-
in 100 mM Tris-HCl, pH 7.0, 100 mM NaCl, 2% (v/v) DMSO, 5 mM dithiothreitol, at 27°C
0.091
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](m-tolyl)methanone
Kis value, mechanism is partial
0.106
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](m-tolyl)methanone
Ki value, mechanism is partial
0.031
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](o-tolyl)methanone
partial mechanism, Ki value
0.036
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](o-tolyl)methanone
partial mechanism, Kis value
0.02
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](m-tolyl)methanone
partial mechanism, Kis value
0.05
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](m-tolyl)methanone
partial mechanism, Ki value
0.057
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](o-tolyl)methanone
Kis value, mechanism is partial
0.312
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](o-tolyl)methanone
Ki value, mechanism is partial
0.061
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](p-tolyl)methanone
Ki value, mechanism is partial
0.104
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](p-tolyl)methanone
Kis value, mechanism is partial
0.00061
9-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]-7,9-dihydro-1H-purine-2,6,8(3H)-trione
-
pH 7.5, 37°C
0.00061
9-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]-7,9-dihydro-1H-purine-2,6,8(3H)-trione
-
in 100 mM Tris-HCl, pH 7.0, 100 mM NaCl, 2% (v/v) DMSO, 5 mM dithiothreitol, at 27°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000013
N-[2,4-dioxo-6-(ribitylamino)-1,2,3,4-tetrahydropyrimidin-5-yl]oxalamic acid ethyl ester
Escherichia coli
-
pH 7.0, 27°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
trimer
subunit fold and arrangement, beta-barrel capped by short alpha-helices on each side, overview
trimer
additional information
trimer
-
folding topology, the active site can be formed at the subunit interface
additional information
each subunit of the homotrimer consists of 2 domains
additional information
-
each subunit of the homotrimer consists of 2 domains
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant homodimeric N-terminal enzyme domain in complex with riboflavin, 7 mg/ml protein in 70 mM sodium potassium phosphate, pH 7.0, and 100 mM sodium chloride, X-ray diffraction structure determination and analysis at 2.6 A resolution, molecular modeling
modeling for the binding of two molecules of inhibitor 5-(4-phosphonobutyryl)amino-6-D-ribitylaminouracil in the active site
-
structure determination by multiwavelength anomalous diffraction method, modeling
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A43L
-
decrease in affinity for substrate 6,7-dimethyl-8-ribityllumazine. A43L replacement causes substantial perturbation of the overall binding site topology
C48S
-
mutation in the activity cavity, causes significant 19F NMR chemical shift modulation of trifluoromethyl derivatives of 6,7-dimethyl-8-ribityllumazine in complex with the protein. Replacement of C48 changes the electron density topology in the N-terminal substrate binding site in the vicinity of C-6 and C-7 atoms of bound ligand
D143G
-
site-directed mutagenesis, soluble protein, too unstable to be purified
D143N
-
site-directed mutagenesis, soluble protein, too unstable to be purified
F2A
H102Q
N181G
-
site-directed mutagenesis, soluble protein, too unstable to be purified
S41A
T3R
-
site-directed mutagenesis, slightly reduced activity, low expression rate
T50A
-
production by site-directed mutagenesis, replacement of threonine residue with alanine decreases the acidity of protein-bound by 1-2 orders of magnitude
T67A
-
production by site-directed mutagenesis, replacement of threonine residue with alanine decreases the acidity of protein-bound by 1-2 orders of magnitude
Y133A
-
site-directed mutagenesis, soluble protein, too unstable to be purified
additional information
F2A
-
nearly inactive mutant, comparison of kinetics for wild-type and mutant enzymes
H102Q
-
highly reduced activity compared to the wild-type enzyme, comparison of kinetics for wild-type and mutant enzymes
S41A
-
site-directed mutagenesis, mutant produces a dimeric pentacyclic reaction intermediate, i.e. compound Q, which can be cleaved in 2 different ways by the enzyme
additional information
-
recombinant sequence segment 1-97 forms a homodimer that can bind riboflavin, 6,7-dimethyl-8-ribityllumazine, and trifluoromethyl-substituted 8-ribityllumazine derivatives, and is required for ligand binding, recombinant sequence segment 101-213 is unstable and only partially involved in riboflavin binding
additional information
-
5 mutants genes cannot be expressed recombinantly in Escherichia coli: C48S, T50R, T67R, T148R, T165R
additional information
-
a F2DELTA deletion mutant construct has no remaining activity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
cloning of sequence segments of residues 1-97 and 101-213, and expression in Escherichia coli
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
riboflavin synthase is a target for the design of potential antibiotics
medicine
-
enzyme is an attractive target for antimicrobial agents, since it is nonexistent in humans
additional information
additional information
the enzyme is a target for development of antimicrobial drugs
additional information
-
the enzyme is a target for development of antimicrobial drugs
additional information
-
mutant C48S of the N-terminal domain is used as tool for high throughput screening system for searching for inhibitory compounds for riboflavin synthase activity
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Plaut, G.W.E.
Studies on the nature of the enzymic conversion of 6,7-dimethyl-8-ribityllumazine to riboflavin
J. Biol. Chem.
238
2225-2243
1963
Eremothecium gossypii, Saccharomyces cerevisiae, Escherichia coli, Eremothecium gossypii AG33
Plaut, G.W.E.; Harvey, R.A.
The enzymatic synthesis of riboflavin
Methods Enzymol.
18B
515-538
1971
Klebsiella aerogenes, Eremothecium gossypii, Bacillus subtilis, Saccharomyces cerevisiae, Escherichia coli, Lactiplantibacillus plantarum, Neurospora crassa, Pseudomonas sp.
-
Harzer, G.; Rokos, H.; Otto, M.K.; Bacher, A.; Ghisla, S.
Biosynthesis of riboflavin. 6,7-Dimethyl-8-ribityllumazine 5-phosphate is not a substrate for riboflavin synthase
Biochim. Biophys. Acta
540
48-54
1978
Bacillus subtilis, Escherichia coli
Bacher, A.; Baur, R.; Eggers, U.; Harders, H.D.; Otto, M.K.; Schnepple, H.
Riboflavin synthases of Bacillus subtilis. Purification and properties
J. Biol. Chem.
255
632-637
1980
Bacillus licheniformis, Bacillus subtilis, Escherichia coli, Escherichia coli B / ATCC 11303, Lactiplantibacillus plantarum, Moorella thermoacetica, Paenibacillus polymyxa, Priestia megaterium, Pseudomonas iodinum, Rhodococcus ruber, Saccharomyces cerevisiae, Streptomyces venezuelae
Illarionov, B.; Kemter, K.; Eberhardt, S.; Richter, G.; Cushman, M.; Bacher, A.
Riboflavin synthase of Escherichia coli. Effect of single amino acid substitutions on reaction rate and ligand binding properties
J. Biol. Chem.
276
11524-11530
2001
Escherichia coli
Truffault, V.; Coles, M.; Diercks, T.; Abelmann, K.; Eberhardt, S.; Luttgen, H.; Bacher, A.; Kessler, H.
The solution structure of the N-terminal domain of riboflavin synthase
J. Mol. Biol.
309
949-960
2001
Escherichia coli (P0AFU8), Escherichia coli
Liao, D.I.; Wawrzak, Z.; Calabrese, J.C.; Viitanen, P.V.; Jordan, D.B.
Crystal structure of riboflavin synthase
Structure
9
399-408
2001
Escherichia coli, no activity in Homo sapiens
Eberhardt, S.; Zingler, N.; Kemter, K.; Richter, G.; Cushman, M.; Bacher, A.
Domain structure of riboflavin synthase
Eur. J. Biochem.
268
4315-4323
2001
Escherichia coli
Cushman, M.; Yang, D.; Gerhardt, S.; Huber, R.; Fischer, M.; Kis, K.; Bacher, A.
Design, synthesis, and evaluation of 6-carboxyalkyl and 6-phosphonoxyalkyl derivatives of 7-oxo-8-ribitylaminolumazines as inhibitors of riboflavin synthase and lumazine synthase
J. Org. Chem.
67
5807-5816
2002
Escherichia coli
Cushman, M.; Yang, D.; Mihalic, J.T.; Chen, J.; Gerhardt, S.; Huber, R.; Fischer, M.; Kis, K.; Bacher, A.
Incorporation of an amide into 5-phosphonoalkyl-6-D-ribitylaminopyrimidinedione lumazine synthase inhibitors results in an unexpected reversal of selectivity for riboflavin synthase vs lumazine synthase
J. Org. Chem.
67
6871-6877
2002
Escherichia coli
Fischer, M.; Romisch, W.; Illarionov, B.; Eisenreich, W.; Bacher, A.
Structures and reaction mechanisms of riboflavin synthases of eubacterial and archaeal origin
Biochem. Soc. Trans.
33
780-784
2005
Arabidopsis thaliana, Escherichia coli, Methanocaldococcus jannaschii, Methanothermobacter thermautotrophicus, Schizosaccharomyces pombe
Illarionov, B.; Haase, I.; Fischer, M.; Bacher, A.; Schramek, N.
Pre-steady-state kinetic analysis of riboflavin synthase using a pentacyclic reaction intermediate as substrate
Biol. Chem.
386
127-136
2005
Escherichia coli
Illarionov, B.; Haase, I.; Bacher, A.; Fischer, M.; Schramek, N.
Presteady state kinetic analysis of riboflavin synthase
J. Biol. Chem.
278
47700-47706
2003
Escherichia coli
Meining, W.; Eberhardt, S.; Bacher, A.; Ladenstein, R.
The structure of the N-terminal domain of riboflavin synthase in complex with riboflavin at 2.6 A resolution
J. Mol. Biol.
331
1053-1063
2003
Escherichia coli (P0AFU8), Escherichia coli
Lee, C.Y.; Illarionov, B.; Woo, Y.E.; Kemter, K.; Kim, R.R.; Eberhardt, S.; Cushman, M.; Eisenreich, W.; Fischer, M.; Bacher, A.
Ligand binding properties of the N-terminal domain of riboflavin synthase from Escherichia coli
J. Biochem. Mol. Biol.
40
239-246
2007
Escherichia coli
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
Escherichia coli, Mycobacterium tuberculosis
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
Escherichia coli
Kim, R.R.; Illarionov, B.; Joshi, M.; Cushman, M.; Lee, C.Y.; Eisenreich, W.; Fischer, M.; Bacher, A.
Mechanistic insights on riboflavin synthase inspired by selective binding of the 6,7-dimethyl-8-ribityllumazine exomethylene anion
J. Am. Chem. Soc.
132
2983-2990
2010
Escherichia coli
Zhao, Y.; Bacher, A.; Illarionov, B.; Fischer, M.; Georg, G.; Ye, Q.Z.; Fanwick, P.E.; Franzblau, S.G.; Wan, B.; Cushman, M.
Discovery and development of the covalent hydrates of trifluoromethylated pyrazoles as riboflavin synthase inhibitors with antibiotic activity against Mycobacterium tuberculosis
J. Org. Chem.
74
5297-5303
2009
Mycobacterium tuberculosis, Escherichia coli (P0AFU8), Escherichia coli
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
Escherichia coli, Mycobacterium tuberculosis
Kim, R.; Yi, J.; Nam, K.; Ko, K.; Lee, C.
Spectrofluorometric characteristics of the N-terminal domain of riboflavin synthase
Korean J. Microbiol.
47
14-21
2011
Escherichia coli
-
EXTERNAL LINKS (specific for EC-Number 2.5.1.9)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
