Information on EC 2.5.1.9 - riboflavin synthase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea

EC NUMBER
COMMENTARY
2.5.1.9
-
RECOMMENDED NAME
GeneOntology No.
riboflavin synthase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
reaction mechanism
-
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
reaction mechanism
-
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
reaction mechanism
-
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
reaction mechanism
-
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
reaction mechanism
-
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
formation of riboflavin by the lumazine synthase/riboflavin synthase complex follows a leaky channel model
-
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
reaction mechanism; substrate binding site
-
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
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
show the reaction diagram
active site
-
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
reaction mechanism; substrate binding site
Q9Y7P0
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
catalytic mechanism, stereochemistry
-
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
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
show the reaction diagram
catalytic mechanism, stereochemistry, pentacyclic reaction intermediate, which is diastereomeric to the reaction intermediate of the enzyme from Escherichia coli
-
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
catalytic mechanism, stereochemistry
-
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
pentacyclic reaction intermediate
-
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
detailed catalytic mechanism, Cys48 is involved
Q9Y7P0, -
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
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
show the reaction diagram
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
show the reaction diagram
reaction mechanism
Eremothecium gossypii AG33
-
-
2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
dismutation
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
flavin biosynthesis I (bacteria and plants)
-
flavin biosynthesis II (archaea)
-
flavin biosynthesis III (fungi)
-
Metabolic pathways
-
Riboflavin metabolism
-
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).
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
heavy riboflavin synthase
-
bifunctional enzyme complex that catalyzes formation of riboflavin from 5-amino-6-ribityl-amino-2,4-pyrimidinedione and 3,4-dihydroxy-2-butanone
light riboflavin synthase
-
-
-
-
RibD
I7GUL1
-
riboflavin synthase
-
-
riboflavin synthase
-
-
riboflavin synthetase
-
-
-
-
riboflavin synthetase
I7GUL1
-
riboflavin synthetase
L0C7R1
-
riboflavine synthase
-
-
-
-
riboflavine synthetase
-
-
-
-
synthase, riboflavin
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9075-82-5
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
AY604007, GenBank synthetic gene
-
-
Manually annotated by BRENDA team
contains heavy and light form of the enzyme
-
-
Manually annotated by BRENDA team
contains heavy and light form of the enzyme
-
-
Manually annotated by BRENDA team
contains heavy and light form of the enzyme; H94) (flavinogenic), H322 (flavinogenic), (H52, Rib-), (107,Rib-), ATCC 6051, ATCC 6633, B23; heavy and light enzyme form
-
-
Manually annotated by BRENDA team
heavy and light enzyme form; mutant WA 45
-
-
Manually annotated by BRENDA team
lumazine synthase/riboflavin synthase complex, the alpha subunit carries riboflavin synthase activity
-
-
Manually annotated by BRENDA team
pure enzyme from mutant strain H94
-
-
Manually annotated by BRENDA team
purified enzyme
-
-
Manually annotated by BRENDA team
strain AG33
-
-
Manually annotated by BRENDA team
Eremothecium gossypii AG33
strain AG33
-
-
Manually annotated by BRENDA team
gene ribC
-
-
Manually annotated by BRENDA team
selenomethionine containing enzyme
-
-
Manually annotated by BRENDA team
strain ATCC 9637
-
-
Manually annotated by BRENDA team
strain ATCC 8005
-
-
Manually annotated by BRENDA team
AY442958, GenBank synthetic gene
-
-
Manually annotated by BRENDA team
gene ribC; Marburg strain
SwissProt
Manually annotated by BRENDA team
Methanothermobacter thermautotrophicus Marburg
Marburg strain
SwissProt
Manually annotated by BRENDA team
bitter melon
UniProt
Manually annotated by BRENDA team
contains heavy and light form of the enzyme
-
-
Manually annotated by BRENDA team
no activity in Homo sapiens
-
-
-
Manually annotated by BRENDA team
contains heavy and light form of the enzyme
-
-
Manually annotated by BRENDA team
Pseudomonas iodinum
-
-
-
Manually annotated by BRENDA team
alpha-chain; var. pombe, ATCC 16491
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
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
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
show the reaction diagram
-
-
-
-
r
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
show the reaction diagram
-
-
-
-
?
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
show the reaction diagram
-
-
catalysed by the alpha-subunit, which forms a trimer surrounded by an icosahedral capsid of 60 beta subunits producing substrate 6,7-dimethyl-8-(1-D-ribityl)lumazine
-
?
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
show the reaction diagram
-
dismutation
riboflavin binding site structure
-
?
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
show the reaction diagram
-
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
show the reaction diagram
-
ultimate step in the biosynthesis of riboflavin, i.e. vitamin B2, the precursor of flavin cofactors
-
-
?
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
show the reaction diagram
Q9Y7P0, -
ultimate step in the biosynthesis of riboflavin, pathway overview
-
-
r
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
show the reaction diagram
-, Q58584
ultimate step in the biosynthesis of riboflavin, pathway overview, evolution of vitamin B2 biosynthesis
-
-
?
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
show the reaction diagram
-
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
show the reaction diagram
-
mechanistical complex dismutation
-
-
r
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
show the reaction diagram
-
mechanistically complex dismutation
-
-
r
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
show the reaction diagram
Q9Y7P0, -
mechanistically complex dismutation
-
-
r
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
show the reaction diagram
-, Q58584
transfer of a 4-carbon fragment
-
-
?
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
?
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
?
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-, I7GUL1
-
-
-
?
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
enzyme catalyzes the transfer of a four-carbon unit between 2 molecules of the substrate, 6,7-dimethyl-8-ribityllumazine
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
P0AFU8
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-, ?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
ir
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-, ?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
Q9Y7P0, -
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
Q9Y7P0, -
-
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-, ?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-, ?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-, ?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-, ?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-, ?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
Pseudomonas iodinum
-
-
-
-
-, ?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-, Q59587
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-, Q59587
-
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
P0AFU8
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-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
i.e. 6,7-dimethyl-8-(1'-D-ribityl)lumazine
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
i.e. 6,7-dimethyl-8-(1'-D-ribityl)lumazine
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
biosynthetic pathway
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
Methanothermobacter thermautotrophicus Marburg
Q59587
-
-
-
-, ?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
Eremothecium gossypii AG33
-
-
-
-
-, ?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + a compound related to 4-ribitylamino-2,5,6-trihydroxypyrimidine
show the reaction diagram
Saccharomyces cerevisiae, Eremothecium gossypii, Eremothecium gossypii AG33
-
-
-
?
6,7-dimethyl-8-[1'-(5'-deoxy-D-ribityl)]lumazine + 6,7-dimethyl-8-[1'-(5'-deoxy-D-ribityl)]lumazine
5'-deoxyriboflavin + ?
show the reaction diagram
-
-
-
?
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
overview
-
-
-
additional information
?
-
Q9Y7P0, -
structure-function relationship
-
-
-
additional information
?
-
-
no activity with lumazine 5'-phosphate
-
-
-
additional information
?
-
-, Q59587
no activity with lumazine 5'-phosphate
-
-
-
additional information
?
-
-
beta-subunit of heavy riboflavin synthase catalyzes the formation of 6,7-dimethyl-8-ribityllumazine from 5-amino-6-ribitylamino-2,4-pyrimidinedione and a carbohydrate phosphate
-
-
-
additional information
?
-
-
dismutation of 6,7-dimethyl-8-ribityllumazine yielding riboflavin and 5-amino-6-ribitylamino-2,4-pyrimidinedione is catalyzed by the alpha-subunit
-
-
-
additional information
?
-
-
salvage cycle for the by-product of the reaction is involved in the de novo synthesis of riboflavin
-
-
-
additional information
?
-
-
archaeal enzymes have diverged early in evolution from a common ancestor
-
-
-
additional information
?
-
-
vitamin B2 biosynthetic pathway evolution, hypothetical gene duplication conductive to the 2-domain architecture occurring very early in evolution
-
-
-
additional information
?
-
-
active with the dimeric pentacyclic reaction intermediate as substrate
-
-
-
additional information
?
-
-, Q58584
activity with different isotopomers, stereochemistry, overview
-
-
-
additional information
?
-
-
no activity with the dimeric pentacyclic reaction intermediate as substrate
-
-
-
additional information
?
-
Q9Y7P0, -
substrate binding structure and catalytic mechanism by NMR analysis and protein perturbation studies using fluoro-substituted reaction intermediate analogues, i.e. 2 epimers of 6,7-bis(trifluoromethyl)-8-ribityllumazine hydrate, 6-trifluoromethyl-7-oxo-8-ribityllumazine, 6-carboxyethyl-7-oxo-8-ribityllumazine, and 5-nitro-6-ribitylamino-2,4-pyrimidinedione, overview
-
-
-
additional information
?
-
-
utilization of the pentacyclic reaction intermediate as substrate
-
-
-
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
?
-
Methanothermobacter thermautotrophicus Marburg
Q59587
no activity with lumazine 5'-phosphate
-
-
-
additional information
?
-
Eremothecium gossypii AG33
-
overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
show the reaction diagram
-
-
-
-
r
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
show the reaction diagram
-
-
-
-
?
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
show the reaction diagram
-
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
show the reaction diagram
-
ultimate step in the biosynthesis of riboflavin, i.e. vitamin B2, the precursor of flavin cofactors
-
-
?
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
show the reaction diagram
Q9Y7P0, -
ultimate step in the biosynthesis of riboflavin, pathway overview
-
-
r
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 5-amino-6-ribitylamino-2,4-(1H,3H)-pyrimidinedione
show the reaction diagram
-, Q58584
ultimate step in the biosynthesis of riboflavin, pathway overview, evolution of vitamin B2 biosynthesis
-
-
?
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
?
6,7-dimethyl-8-(1-D-ribityl)lumazine
riboflavin + 4-(1-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
enzyme catalyzes the transfer of a four-carbon unit between 2 molecules of the substrate, 6,7-dimethyl-8-ribityllumazine
-
-
?
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
P0AFU8
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
Q9Y7P0, -
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-, Q59587
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
i.e. 6,7-dimethyl-8-(1'-D-ribityl)lumazine
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
-
biosynthetic pathway
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
Methanothermobacter thermautotrophicus Marburg
Q59587
-
-
-
-
6,7-dimethyl-8-ribityllumazine + 6,7-dimethyl-8-ribityllumazine
riboflavin + 4-(1'-D-ribitylamino)-5-amino-2,6-dihydroxypyrimidine
show the reaction diagram
Eremothecium gossypii AG33
-
-
-
-
-
additional information
?
-
-
salvage cycle for the by-product of the reaction is involved in the de novo synthesis of riboflavin
-
-
-
additional information
?
-
-
archaeal enzymes have diverged early in evolution from a common ancestor
-
-
-
additional information
?
-
-
vitamin B2 biosynthetic pathway evolution, hypothetical gene duplication conductive to the 2-domain architecture occurring very early in evolution
-
-
-
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 ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
additional information
-
no cofactor requirement
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Mg2+
-, Q59587
absolute requirement
Mg2+
-, Q58584
preferred cation; preferred cation
Mn2+
-, Q58584
preferred cation; preferred cation
additional information
-
no effect by Ba2+, Co2+
additional information
-, Q58584
divalent cations are required for maximal activity; divalent cations are required for maximal activity
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
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-Amino-4,6-dihydroxy-8-D-ribityl-7-pteridinone
-
-
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)acetamide
-
uncompetitive inhibition
-
2-chloro-N-(2,4-dioxo-6-((2S,3S,4R)-2,3,4,5-tetrahydroxypentylamino)-1,2,3,4-tetrahydropyrimidin-5-yl)propanamide
-
-
-
2-chloro-N-(2,4-dioxo-6-((2S,3S,4R)-2,3,4,5-tetrahydroxypentylamino)-1,2,3,4-tetrahydropyrimidin-5-yl)propanamide
-
competitive inhibition
-
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
5,5'-dithiobis(2-nitrobenzoate)
-
-
5,6,7,8-Tetrahydro-9-(1'-D-ribityl)isoalloxazine
-
-
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
-
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
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-amino-6-[[(2R,3R,4R)-2,3,4,5-tetrahydroxypentyl]sulfanyl]pyrimidine-2,4(1H,3H)-dione
-
competitive inhibition
5-nitro-6-[(3S,4S,5R)-3,4,5,6-tetrahydroxyhexyl]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
-
competitive 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,3R,4R)-2,3,4,5-tetrahydroxypentyl]oxy]pyrimidine-2,4(1H,3H)-dione
-
partial inhibition
5-nitro-6-[[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino]pyrimidine-2,4(1H,3H)-dione
-
mixed-type inhibition
5-nitro-6-[[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino]pyrimidine-2,4(1H,3H)-dione
-
competitive inhibition
6,7-dihydroxy-8-ribityllumazine
-
-
6,7-dimethyl-8-(1'-D-xylityl)lumazine
-
-
6-Methyl-7-hydroxy-8-ribityllumazine
-
-
6-Methyl-7-hydroxy-8-ribityllumazine
-
-
6-Methyl-7-hydroxy-8-ribityllumazine
-
-
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-6-(2-carboxyethyl)-8-(1-D-ribityl)lumazine
-
-
7-hydroxy-6-(D-1,2-dihydroxyethyl)-8-(1-D-ribityl)lumazine
-
-
7-Hydroxy-6-(L-1,2-dihydroxyethyl)-8-(1-D-ribityl)lumazine
-
i.e. photolumazine A
7-hydroxy-6-(p-hydroxyphenyl)-8-(1-D-ribityl)lumazine
-
-
-
7-Hydroxy-6-hydroxymethyl-8-(1-D-ribityl)lumazine
-
photolumazine B
7-hydroxy-7-methyl-8-((2S,3S,4R)-2,3,4,5-tetrahydroxypentyl)-7,8-dihydropteridin-2,4,6(1H,3H,5H)-trione
-
-
-
7-hydroxy-7-methyl-8-((2S,3S,4R)-2,3,4,5-tetrahydroxypentyl)-7,8-dihydropteridin-2,4,6(1H,3H,5H)-trione
-
competitive inhibition
-
7-Hydroxy-8-(1-D-ribityl)lumazine
-
i.e. photolumazine
8-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]-5,8-dihydropteridine-2,4,6,7(1H,3H)-tetrone
-
competitive inhibition
8-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]-5,8-dihydropteridine-2,4,6,7(1H,3H)-tetrone
-
-
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
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
-
-
Avidin
-
moderately, no prevention by biotin
-
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 [(2,4-dioxo-6-[[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino]-1,2,3,4-tetrahydropyrimidin-5-yl)amino](oxo)acetate
-
-
ethyl [(6-chloro-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)amino](oxo)acetate
-
-
ethyl [(6-chloro-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)amino](oxo)acetate
-
uncompetitive inhibition
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)methacrylamide
-
uncompetitive inhibition
-
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-((2R,3R,4R)-2,3,4,5-tetrahydroxypentylthio)-1,2,3,4-tetrahydropyrimidin-5-yl)propionamide
-
uncompetitive inhibition
-
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)isobutyramide
-
uncompetitive inhibition
-
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)methacrylamide
-
uncompetitive inhibition
-
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,3R,4R)-2,3,4,5-tetrahydroxypentyloxy)-1,2,3,4-tetrahydropyrimidin-5-yl)propionamide
-
uncompetitive inhibition
-
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-tetrahydroxypentylamino)-1,2,3,4-tetrahydropyrimidin-5-yl)-3,3,3-trifluoropropanamide
-
uncompetitive inhibition
-
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)-2-methylpropanamide
-
-
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-(2,4-dioxo-6-[[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino]-1,2,3,4-tetrahydropyrimidin-5-yl)propanamide
-
-
N-(6-chloro-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-methacrylamide
-
-
-
N-(6-chloro-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-methacrylamide
-
uncompetitive inhibition
-
N-(6-chloro-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)propanamide
-
-
N-(6-chloro-2,4-dioxo-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-((2S,3S,4R)-2,3,4,5-tetrahydroxypentylamino]-1,2,3,4-tetrahydropyrimidin-5-yl)methacrylamide
-
partial inhibition
-
N-[2,4-dioxo-6-(ribitylamino)-1,2,3,4-tetrahydropyrimidin-5-yl]oxalamic acid ethyl ester
-
mixed type inhibition
p-chloromercuribenzenesulfonate
-
reversible by cysteine or 2-mercaptoethanol
p-chloromercuribenzoate
-
-
riboflavin
-
product inhibition, Saccharomyces cerevisiae
riboflavin
-
sigmoidal product inhibition
[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
additional information
-
no effect by Ba2+, Co2+, EDTA
-
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
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2,3-Dimercapto-1-propanol
-
enhances activity
2-mercaptoethanol
-
enhances activity
N-acetylcysteine
-
enhances activity
SO32-
-
enhances activity
SO32-
-
enhances activity; sodium sulfite
SO32-
-
enhances activity
Diacetyl
-
activates
additional information
-
assay carried out under reducing condition to avoid side reactions and because of the lability of the enzyme in presence of O2
-
additional information
-
no requirement for a cofactor
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.01
-
6,7-dimethyl-8-(1'-D-ribityl)lumazine
-
pH 7.0
0.013
-
6,7-dimethyl-8-(1'-D-ribityl)lumazine
-
heavy enzyme
0.014
-
6,7-dimethyl-8-(1'-D-ribityl)lumazine
-
light enzyme
0.029
-
6,7-dimethyl-8-(1'-D-ribityl)lumazine
-
-
0.04
-
6,7-dimethyl-8-(1'-D-ribityl)lumazine
-
-
0.045
-
6,7-dimethyl-8-(1'-D-ribityl)lumazine
-
pH 7.5
0.13
-
6,7-dimethyl-8-(1'-D-ribityl)lumazine
-
-
0.13
-
6,7-dimethyl-8-(1'-D-ribityl)lumazine
-
pH 7.0, 37C
0.0057
-
6,7-dimethyl-8-(1-D-ribityl)lumazine
Q9Y7P0, -
pH 7.2, 37C, recombinant enzyme
additional information
-
additional information
-
Km is temperature-dependent
-
additional information
-
additional information
-
sigmoidal kinetics is observed with mixtures of artifactual beta 60 capsids and alpha subunit trimers. Km value for lumazine of the lumazine synthase/riboflavin synthase complex is about 10 times larger as compared to light riboflavin synthase consisting of alpha subunits, without lumazine synthase activity
-
additional information
-
additional information
-
stopped flow and quenched flow kinetics of wild-type enzyme and mutant S41A
-
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
-
kinetics, numerical simulation, recombinant enzyme
-
additional information
-
additional information
-
presteady state kinetic analysis, single turnover conditions, transient stopped flow and quenched flow kinetics measurements of the pentacyclic reaction intermediate
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1.2
-
6,7-dimethyl-8-(1'-D-ribityl)lumazine
-
heavy enzyme, Bacillus subtilis H94
2
-
6,7-dimethyl-8-(1'-D-ribityl)lumazine
-
light enzyme, Bacillus subtilis H94
0.001
-
6,7-dimethyl-8-(1-D-ribityl)lumazine
-
pH 6.9, 25C, recombinant mutant H102Q, steady-state conditions
0.027
-
6,7-dimethyl-8-(1-D-ribityl)lumazine
-
25C, recombinant enzyme
0.267
-
6,7-dimethyl-8-(1-D-ribityl)lumazine
-
pH 6.9, 25C, recombinant wild-type enzyme, steady-state conditions
0.00833
-
6,7-dimethyl-8-ribityllumazine
-
per subunit
0.019
-
6,7-dimethyl-8-ribityllumazine
-
pH 7.0, 37C
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
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 27C
0.0025
-
2,4-dioxo-6-[[(2R,3R,4R)-2,3,4,5-tetrahydroxypentyl]sulfanyl]-1,2,3,4-tetrahydropyrimidin-5-aminium chloride
-
pH 7.0, 27C
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, 27C
0.314
-
2-chloro-N-(2,4-dioxo-6-((2S,3S,4R)-2,3,4,5-tetrahydroxypentylamino)-1,2,3,4-tetrahydropyrimidin-5-yl)propanamide
-
in 100 mM Tris-HCl, pH 7.0, 100 mM NaCl, 2% (v/v) DMSO, 5 mM dithiothreitol, at 27C
-
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, 37C
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, 37C
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, 37C
0.16
-
5-(4-phosphonobutyryl)amino-6-D-ribitylaminouracil
-
pH 7.5, 37C
0.0068
-
5-(4-phosphonopentyryl)amino-6-D-ribitylaminouracil
-
pH 7.5, 37C
0.19
-
5-(5-phosphonoxyvaleryl)amino-6-D-ribitylaminouracil
-
pH 7.5, 37C
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, 37C
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, 37C
0.0025
-
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 27C
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 27C
0.0084
-
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 27C
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 27C
0.00056
-
5-nitro-6-[[(2R,3R,4R)-2,3,4,5 tetrahydroxypentyl]sulfanyl]pyrimidine-2,4(1H,3H)-dione
-
pH 7.0, 27C
0.0027
-
5-nitro-6-[[(2R,3R,4R)-2,3,4,5 tetrahydroxypentyl]sulfanyl]pyrimidine-2,4(1H,3H)-dione
-
pH 7.0, 27C
0.00056
-
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 27C
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 27C
0.036
-
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 27C
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 27C
0.0042
-
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 27C
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 27C
0.0029
-
6-Methyl-7-hydroxy-8-ribityllumazine
-
-
0.18
-
6-Methyl-7-hydroxy-8-ribityllumazine
-
-
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, 37C
0.027
-
7-hydroxy-6-(2-carboxyethyl)-8-(1-D-ribityl)lumazine
-
-
0.017
-
7-hydroxy-6-(D-1,2-dihydroxyethyl)-8-(1-D-ribityl)lumazine
-
-
0.017
-
7-Hydroxy-6-(L-1,2-dihydroxyethyl)-8-(1-D-ribityl)lumazine
-
-
0.028
-
7-hydroxy-6-(p-hydroxyphenyl)-8-(1-D-ribityl)lumazine
-
-
-
0.003
-
7-Hydroxy-6-hydroxymethyl-8-(1-D-ribityl)lumazine
-
-
0.00074
-
7-hydroxy-7-methyl-8-((2S,3S,4R)-2,3,4,5-tetrahydroxypentyl)-7,8-dihydropteridin-2,4,6(1H,3H,5H)-trione
-
in 100 mM Tris-HCl, pH 7.0, 100 mM NaCl, 2% (v/v) DMSO, 5 mM dithiothreitol, at 27C
-
0.011
-
7-Hydroxy-8-(1-D-ribityl)lumazine
-
-
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 27C
0.00061
-
9-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]-7,9-dihydro-1H-purine-2,6,8(3H)-trione
-
pH 7.5, 37C
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 27C
0.052
-
N-[2,4-dioxo-6-((2S,3S,4R)-2,3,4,5-tetrahydroxypentylamino]-1,2,3,4-tetrahydropyrimidin-5-yl)methacrylamide
-
in 100 mM Tris-HCl, pH 7.0, 100 mM NaCl, 2% (v/v) DMSO, 5 mM dithiothreitol, at 27C
-
0.014
-
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](m-tolyl)methanone
-
Ki value, mechanism is partial
0.038
-
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](m-tolyl)methanone
-
Kis value, mechanism is partial
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
0.0087
-
[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
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
0.01
-
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](p-tolyl)methanone
-
Kis value, mechanism is partial
0.016
-
[3-(4-chlorophenyl)-5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](p-tolyl)methanone
-
Ki value, mechanism is partial
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
-
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](m-tolyl)methanone
-
partial mechanism, Kis value
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
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
0.05
-
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](m-tolyl)methanone
-
partial mechanism, Ki value
0.0067
-
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](o-tolyl)methanone
-
Ki value, mechanism is partial
0.016
-
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](o-tolyl)methanone
-
Kis value, mechanism is partial
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
0.01
-
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](p-tolyl)methanone
-
Kis value, mechanism is partial
0.023
-
[5-(4-chlorophenyl)-5-hydroxy-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl](p-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
0.0000013
-
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 27C
additional information
-
additional information
-
inhibition kinetics, recombinant enzyme
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0000013
-
N-[2,4-dioxo-6-(ribitylamino)-1,2,3,4-tetrahydropyrimidin-5-yl]oxalamic acid ethyl ester
-
pH 7.0, 27C
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.00025
-
-
partially purified enzyme
0.0014
-
-
partially purified enzyme
0.002
-
-, Q58584
purified recombinant enzyme, in absence of divalent cations; purified recombinant enzyme, in absence of divalent cations
0.003
-
-
-
0.011
-
-
purified enzyme
0.011
-
-
substrate 6,7-dimethyl-8-(1-D-ribityl)lumazine
0.021
-
-
with substrate compound Q, a dimer of the pentameric reaction intermediate
0.024
-
-, Q58584
purified recombinant enzyme, in presence of divalent cations; purified recombinant enzyme, in presence of divalent cations
0.027
-
-
heavy enzyme
0.027
-
-
heavy enzyme; purified enzyme
0.032
-
-, Q59587
65C; purified recombinant enzyme
0.033
-
-
heavy enzyme
0.045
-
-, Q59587
65C; purified enzyme
0.052
-
-
purified enzyme
0.16
-
-
purified enzyme
0.266
-
-
purified enzyme
0.5
-
-
light enzyme
0.833
-
-
light enzyme
1.2
2.8
-
partially purified enzyme
27
-
Q9Y7P0, -
purified recombinant mutant C48S
158
-
Q9Y7P0, -
purified recombinant wild-type enzyme
179
-
Q9Y7P0, -
purified recombinant mutant S146C
183
-
Q9Y7P0, -
purified recombinant mutant S146A
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
assay method
additional information
-
-
-
additional information
-
-
-
additional information
-
-
various estimation methods
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.9
-
-
assay at
7
-
-, Q58584
assay at; assay at
7.2
-
Q9Y7P0, -
assay at
7.3
-
-
assay at
7.4
-
-
light enzyme, the pH-optimum of the heavy enzyme is similar, detailed measurement is not possible because of instability at elevated pH
7.5
-
-
assay at
7.5
-
-
both lumazine synthase and riboflavin synthase activity
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.4
8.8
-
about 50% of activity maximum at pH 5.4 and 8.8
5.8
8.4
-
about 50% of activity maximum at pH 5.8 and 8.4
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
50
95
-
50C: about 10% of activity maximum, 80C: about 30% of activity maximum, 95C: activity maximum
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
L0C7R1, -
high expression
Manually annotated by BRENDA team
L0C7R1, -
high expression in young leaves
Manually annotated by BRENDA team
Eremothecium gossypii AG33
-
-
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
Schizosaccharomyces pombe (strain 972 / ATCC 24843)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
67500
-
-
recombinant enzyme expressed from synthetic gene, sedimentation equilibrium centrifugation and gel filtration
70000
80000
-
analytical ultracentrifugation
70000
-
-
analytical ultracentrifugation; light enzyme
70000
-
-
light enzyme
70000
-
-
-
75000
-
-
-
88300
-
-, Q58584
sedimentation equilibrium centrifugation, recombinant enzyme; sedimentation equilibrium centrifugation, recombinant enzyme
100000
-
-
heavy riboflavin synthase
100000
-
-
analytical ultracentrifugation; heavy riboflavin synthase
100000
-
-
heavy riboflavin synthase
345000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
Q2VCE7, -
x * 22000, SDS-PAGE
pentamer
-, Q58584
5 * 17500, recombinant enzyme; 5 * 17500, recombinant enzyme
polymer
-
60 * 16000-16200 (beta) + 3 * 23500 (alpha), heavy riboflavin synthase, X-ray studies, analytical ultracentrifugation
polymer
-
60 * 16000-16200 (beta) + 3 * 23500 (alpha), heavy riboflavin synthase, X-ray studies, analytical ultracentrifugation; primary structure of beta subunit
trimer
-
3 * 22043, light enzyme, calculation from amino acid sequence
trimer
-
3 * 23500, light enzyme, SDS-PAGE, subunits not covalently linked
trimer
-
3 * 23000
trimer
-
2 folding topologies, the active site can be formed at the subunit interface or each subunit binds one substrate molecule
trimer
-
folding topology, the active site can be formed at the subunit interface
trimer
-
folding topology, each subunit binds one substrate molecule
trimer
-
3 * 21171, recombinant enzyme expressed from synthetic gene, electrospray mass spectrometry
trimer
Q9Y7P0, -
3 * 23000, sedimentation equilibrium centrifugation
trimer
-
subunit fold and arrangement, beta-barrel capped by short alpha-helices on each side, overview
?
L0C7R1, -
x * 30670, calculated from amino acid sequence
additional information
-
N-terminal structure, ligand binding site
additional information
-
each subunit of the homotrimer consists of 2 domains; N-terminal structure, ligand binding site
additional information
Q9Y7P0
structure model, biological implication
additional information
Q9Y7P0, -
2 similar folding domains per subunit
additional information
Q2VCE7, -
N-terminal sequence is MFTGIVEELGEITAV
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
detailed structure determination and analysis of enzyme complexed with heavy atoms, three-dimensional structure model
-
from 1.3 M sodium/potassium phosphate, pH 8.7, 0.35 mM 5-nitroso-6-(1'-D-ribitylamino)-2,4(1H,3H)-pyrimidinedione, X-ray structure determination and analysis
-
large crystals by vapour diffusion method, initial solution: 0.7 M sodium/potassium phosphate, pH 8.7, 0.3 mM 5-nitroso-6-ribitylamino-2,4(1H,3H)-pyrimidinedione, protein 2 mg/ml, reservoir solution: 1.3 M sodium/potassium phosphate, pH 8.7, X-ray structure determination and analysis
-
modeling for the binding of two molecules of inhibitor 5-(4-phosphonobutyryl)amino-6-D-ribitylaminouracil in the active site
-
molecular modeling of inhibitors to the active site
-
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
-
structure determination by multiwavelength anomalous diffraction method, modeling
-
crystallization of enzyme complexed with 6-carboxyethyl-7-oxo-8-ribityllumazine, sitting drop vapour diffusion method against equal amounts of reservoir solution containing 0.1 M bicine, pH 9.0, 65% v/v 2-mehyl-2,4-pentanediol, enzyme solution: 9 mg/ml, 20 mM TrisHCl, pH 7.0, 0.1 M KCl, 10 molar excess of solid 8, X-ray structure determination and analysis, structure model building and refinement, overview
Q9Y7P0
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4
8
-
0C, stable for several h in presence of a suitable reducing agent
6
10
-
26C, 18 h, stable
6.3
7.6
-
55C, 18 h, stable
additional information
-
-
heavy enzyme is instable at elevated pH
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0
2
-
cold lability, inclusion of 0.01 M sodium sulfite in the solution used in purification prevents inactivation
60
-
-
24 h, no loss of activity, without substrate
80
-
-
1 min, complete loss of activity
85
-
-
10 min, complete loss of activity
92
-
-
1 min, complete loss of activity
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
stable at 26C in 4 M urea for 18 h, 4 M urea completely inactivates at 55C
-
high ionic strength protects yeast enzyme against inactivation
-
reducing agents, e.g. cysteine, ascorbate or Na2SO4 stabilize yeast and spinach enzyme
-
freezing, completely inactivates spinach enzyme
-
reducing agents, e.g. cysteine, ascorbate or Na2SO4 stabilize yeast and spinach enzyme
-
OXIDATION STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
lability in presence of O2
-
637563
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20C, slow decomposition by formation of large beta-subunit aggregates devoid of alpha-subunits
-
solution in 0.1 M phosphate, pH 7.0, 10 mM EDTA and 10 mM sodium sulfite, stable for several months
-
frozen, mycelium, several months without loss of activity
-
4C, 6 months, no loss of activity
-
-20C, completely purified enzyme, stable for several months
-
-90C or in liquid N2, stable for several months
-
frozen, partially purified in dissolved ammonium sulfate precipitation pellet, stable several weeks
-
0-4C, stable for 1 week in presence of saturated ammonium sulfate
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant enzyme from Escherichia coli
-
heavy enzyme
-
heavy enzyme; light enzyme
-
light enzyme
-
partially
-
wild-type enzyme and mutants
-
recombinant enzyme from Escherichia coli to homogeneity; recombinant enzyme from Escherichia coli to homogeneity
-, Q58584
recombinant wild-type and mutant enzymes from Escherichia coli by ion exchange chromatography, ultrafiltration, gel filtration, and hydrophobic interaction chromatography
Q9Y7P0, -
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
phylogenetic analysis, highly effective expression in Escherichia coli by construction of a synthetic gene optimized for heterologous expression by exchange of 59 codons
-
cloning of sequence segments of residues 1-97 and 101-213, and expression in Escherichia coli
-
expression in Escherichia coli
-
expression of beta60 capsid
-
expression of wild-type and mutant enzymes in strain BL21(DE3)
-
recombinant N-terminal domain of riboflavin synthase is prepared
-
ribC hyperexpression strain, DNA sequence determination of mutants
-
optimization of expression in Escherichia coli by construction of a synthetic gene; optimization of expression in Escherichia coli by construction of a synthetic gene, phylogenetic analysis
-, Q58584
DNA and amino acid sequence determination and analysis, functional expression in riboflavin-deficient Escherichia coli mutant BSV23
-, Q59587
DNA and amino acid sequence determination and analysis, subcloning and expression in Escherichia coli strains M15 and XL1-Blue, wild-type and mutant enzymes
Q9Y7P0, -
expression in Escherichia coli
Q2VCE7, -
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
gene expression is up-regulated 5.7fold under iron deficiency
-, I7GUL1
strongest expression levels are observed during the last stage of fruit ripening
L0C7R1, -
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
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
D185L
-
site-directed mutagenesis, low remaining activity
E183G
-
site-directed mutagenesis, reduced activity
E66G
-
site-directed mutagenesis, low remaining activity
E85G
-
site-directed mutagenesis, reduced activity
F2A
-
site-directed mutagenesis, no remaining activity
F2A
-
nearly inactive mutant, comparison of kinetics for wild-type and mutant enzymes
F2Y
-
site-directed mutagenesis, very low remaining activity
H102Q
-
site-directed mutagenesis, very low remaining activity
H102Q
-
highly reduced activity compared to the wild-type enzyme, comparison of kinetics for wild-type and mutant enzymes
H97Q
-
site-directed mutagenesis, low remaining activity
N181G
-
site-directed mutagenesis, soluble protein, too unstable to be purified
N45G
-
site-directed mutagenesis, slightly reduced activity
N83G
-
site-directed mutagenesis, reduced activity
S146G
-
site-directed mutagenesis, low remaining activity
S41A
-
site-directed mutagenesis, very low remaining activity
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
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
T71A
-
site-directed mutagenesis, slightly reduced activity
Y133A
-
site-directed mutagenesis, soluble protein, too unstable to be purified
C48A
Q9Y7P0, -
site-directed mutagenesis, nearly inactive mutant
C48M
Q9Y7P0, -
site-directed mutagenesis, nearly inactive mutant
C48S
Q9Y7P0, -
site-directed mutagenesis, highly decreased activity compared to the wild-type enzyme
S146A
Q9Y7P0, -
site-directed mutagenesis, slightly increased activity compared to the wild-type enzyme
K137A
-
site-directed mutagenesis, low remaining activity
additional information
-
5 mutants genes cannot be expressed recombinantly in Escherichia coli: C48S, T50R, T67R, T148R, T165R; a F2DELTA deletion mutant construct has no remaining activity
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
S146C
Q9Y7P0, -
site-directed mutagenesis, slightly increased activity compared to the wild-type enzyme
additional information
Q2VCE7, -
overexpression in Escherichia coli can suppress the lack of pyrimidine deaminase/reductase in a riboflavin-deficient ribD- strain
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
drug development
-
riboflavin synthase is a target for the design of potential antibiotics
drug development
-
riboflavin synthase is a target for the design of potential antibiotics
pharmacology
Q9Y7P0, -
the enzyme is a target for development of antiinfective drugs
medicine
-
enzyme is an attractive target for antimicrobial agents, since it is nonexistent in humans
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