Information on EC 4.1.2.25 - dihydroneopterin aldolase

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

EC NUMBER
COMMENTARY
4.1.2.25
-
RECOMMENDED NAME
GeneOntology No.
dihydroneopterin aldolase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
2-Amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine = 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine + glycolaldehyde
show the reaction diagram
mechanism
-
2-Amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine = 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine + glycolaldehyde
show the reaction diagram
mechanism
-
2-Amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine = 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine + glycolaldehyde
show the reaction diagram
polarization of the 2'-hydroxy group of the substrate can serve as the initial reaction step for the aldolase
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
elimination
-
-
of an aldehyde, C-C bond cleavage
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
6-hydroxymethyl-dihydropterin diphosphate biosynthesis
-
-
6-hydroxymethyl-dihydropterin diphosphate biosynthesis I
-
-
6-hydroxymethyl-dihydropterin diphosphate biosynthesis II (archaea)
-
-
6-hydroxymethyl-dihydropterin diphosphate biosynthesis III (Chlamydia)
-
-
Folate biosynthesis
-
-
Metabolic pathways
-
-
tetrahydromethanopterin biosynthesis
-
-
SYSTEMATIC NAME
IUBMB Comments
2-amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine glycolaldehyde-lyase (2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine-forming)
-
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
aldolase, dihydroneopterin
-
-
-
-
DHNA
-
-
-
-
DHNA
-
DHNA catalyzes both the cleavage of 7,8-dihydroneopterin to form 6-hydroxymethyl-7,8-dihydropterin and glycolaldehyde and the epimerization of 7,8-dihydroneopterin to form 7,8-dihydro-l-monapterin
DHNA
-
DHNA catalyzes both the cleavage of 7,8-dihydroneopterin to form 6-hydroxymethyl-7,8-dihydropterin and glycolaldehyde and the epimerization of 7,8-dihydroneopterin to form 7,8-dihydro-l-monapterin
DHNA-HPPK
-
DHNA is part of the bifunctional dihydroneopterin aldolase/6 hydroxymethyl-7,8-dihydropterin pyrophosphokinase, also called SulD
dihydroneopterin aldolase
-
-
dihydroneopterin aldolase
-
-
FASA
-
-
-
-
FolB
Escherichia coli MG1655
-
-
-
Rv3607c
P9WNC5
gene name
CAS REGISTRY NUMBER
COMMENTARY
37290-59-8
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
recombinant
Uniprot
Manually annotated by BRENDA team
BL21(DE3)
-
-
Manually annotated by BRENDA team
strain B
-
-
Manually annotated by BRENDA team
strain MG1655
-
-
Manually annotated by BRENDA team
Escherichia coli MG1655
strain MG1655
-
-
Manually annotated by BRENDA team
no activity in mammalia
-
-
-
Manually annotated by BRENDA team
no activity in Plasmodium falciparum
Plasmodium falciparum cell extracts have SHMT and PPPK-DHPS but not DHNA activities
-
-
Manually annotated by BRENDA team
multifunctional Fas enzyme with the activity of the first three enzymes of the folate synthesis pathway: dihydroneopterin aldolase, hydroxymethyldihydropterin pyrophosphokinase and dihydropteroate synthase
-
-
Manually annotated by BRENDA team
cultivar MicroTom
-
-
Manually annotated by BRENDA team
bifunctional enzyme with dihydroneopterin aldolase activity and hydroxymethyldihydropterin pyrophosphokinase activity
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
6-pyruvoyltetrahydropterin synthase paralogs with an active-site glutamate (designated PTPS-III proteins) can functionally replace FolB in vivo
malfunction
Escherichia coli MG1655
-
6-pyruvoyltetrahydropterin synthase paralogs with an active-site glutamate (designated PTPS-III proteins) can functionally replace FolB in vivo
-
physiological function
-
in isoform folA1 conditional mutant germlings incubated at 30C for 16 h, the number of nuclei at is comparable with that of wild type germlings. At the restrictive temperature of 44C, however, 60% of the conidiospores have a single nucleus while wild-type germlings normally undergo two or three nuclear divisions under these conditions. Mutant cells exit from M phase, arrest at 44C, traverse mitosis and G1 phase, and arrest in S phase in the presence of hydroxyurea. The addition of 1.8 mM folic acid does not improve growth of folA1 mutant strains at 44C, nor does it improve their growth at 30C. A mutation in folA can suppress fungal transcription factor crzAD calcium toxicity
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-Amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
2-Amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine + glycolaldehyde
show the reaction diagram
-
-
-
-
2-Amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
2-Amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine + glycolaldehyde
show the reaction diagram
-
-
-
-
2-Amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
2-Amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine + glycolaldehyde
show the reaction diagram
-
-
-
-
2-Amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
2-Amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine + glycolaldehyde
show the reaction diagram
-
-
-
-
2-Amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
2-Amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine + glycolaldehyde
show the reaction diagram
-
-
-
-
2-Amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
2-Amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine + glycolaldehyde
show the reaction diagram
-
-
-
-
2-Amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
2-Amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine + glycolaldehyde
show the reaction diagram
-
-
-
-
2-Amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
2-Amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine + glycolaldehyde
show the reaction diagram
-
-
-
-
2-Amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
2-Amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine + glycolaldehyde
show the reaction diagram
-
not reversible
-
-
2-Amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
?
show the reaction diagram
-
first enzyme in the folate synthesis pathway
-
-
-
2-Amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
?
show the reaction diagram
-
first enzyme in the folate synthesis pathway
-
-
-
2-Amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
?
show the reaction diagram
-
enzyme is involved in the biosynthetic pathway of tetrahydrofolate
-
-
-
2-Amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
?
show the reaction diagram
-
the enzyme is involved in the de novo synthesis of folic acid from guanosine triphosphate
-
-
-
2-Amino-4-hydroxy-6-(L-threo-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
?
show the reaction diagram
-
-
-
-
-
2-Amino-4-hydroxy-6-(L-threo-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
?
show the reaction diagram
-
-
-
-
-
6-hydroxymethyl-7,8-dihydropterin
?
show the reaction diagram
-
-
-
-
?
6-hydroxymethyl-7,8-dihydropterin + glycolaldehyde
7,8-dihydroneopterin + 7,8-dihydromonapterin
show the reaction diagram
P9WNC5
-
reaction is reversible, and C-C bond formation has both 7,8-dihydroneopterin and 7,8-dihydromonapterin as products plus 7,8-dihydroxanthopterin
-
r
7,8-dihydro-L-monapterin
?
show the reaction diagram
-
-
-
-
?
7,8-Dihydromonapterin
?
show the reaction diagram
-
-
-
-
-
7,8-dihydromonapterin
6-hydroxymethyl-7,8-dihydropterin + glycolaldehyde
show the reaction diagram
P9WNC5
-
-
-
r
7,8-dihydroneopterin
6-hydroxymethyl-7,8-dihydropterin + glycolaldehyde
show the reaction diagram
-
-
-
-
?
7,8-dihydroneopterin
6-hydroxymethyl-7,8-dihydropterin + glycolaldehyde
show the reaction diagram
P56740
-
-
-
?
7,8-dihydroneopterin
6-hydroxymethyl-7,8-dihydropterin + glycolaldehyde
show the reaction diagram
-
-
-
-
r
7,8-dihydroneopterin
6-hydroxymethyl-7,8-dihydropterin + glycolaldehyde
show the reaction diagram
-
-
-
?
7,8-dihydroneopterin
6-hydroxymethyl-7,8-dihydropterin + glycolaldehyde
show the reaction diagram
-
-
-
-
?
7,8-dihydroneopterin
6-hydroxymethyl-7,8-dihydropterin + glycolaldehyde
show the reaction diagram
-
-
-
-
r
7,8-dihydroneopterin
6-hydroxymethyl-7,8-dihydropterin + glycolaldehyde
show the reaction diagram
-
-
-
?
7,8-dihydroneopterin
6-hydroxymethyl-7,8-dihydropterin + glycolaldehyde
show the reaction diagram
-
-
-
-
?
7,8-dihydroneopterin
6-hydroxymethyl-7,8-dihydropterin + glycolaldehyde
show the reaction diagram
-
-
-
?
7,8-dihydroneopterin
6-hydroxymethyl-7,8-dihydropterin + glycolaldehyde
show the reaction diagram
-
-
-
-
ir
7,8-dihydroneopterin
6-hydroxymethyl-7,8-dihydropterin + glycolaldehyde
show the reaction diagram
-
-
-
-
?
7,8-dihydroneopterin
6-hydroxymethyl-7,8-dihydropterin + glycolaldehyde
show the reaction diagram
P9WNC5
-
-
-
r
7,8-dihydroneopterin
6-hydroxymethyl-7,8-dihydropterin + glycolaldehyde
show the reaction diagram
-
protonation of the reaction intermediate occurs preferentially in the pro-S-position
-
?
7,8-dihydroneopterin
6-hydroxymethyl-7,8-dihydropterin + glycolaldehyde
show the reaction diagram
Escherichia coli MG1655
-
-
-
-
?
additional information
?
-
-
also catalyzes the epimerization of carbon 2' of dihydroneopterin and dihydromonapterin
-
-
-
additional information
?
-
-
no activity with: 2-amino-4-hydroxy-6-(D-threo-1,2,3-trihydroxypropyl)-7,8-dihydropteridine and 2-amino-4-hydroxy-6-(L-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
-
-
-
additional information
?
-
-
enzyme also mediates the epimerisation of 7,8-dihydroneopterin to 7,8-dihydromonapterin
-
?
additional information
?
-
-
enzyme in folate biosynthesis
-
?
additional information
?
-
P9WNC5
enzyme can utilize both dihydroneopterin and 7,8-dihydromonapterin as substrates to generate 6-hydroxymethyl-7,8-dihydropterin. The reaction generates three different pterin products, one of which is not produced by other wild-type dihydroneopterin aldolases. The enzyme-substrate complex partitions 51% in the first turnover to form the aldolase products, 24% to the epimerase product and 25% to the oxygenase products. The aldolase reaction is strongly pH dependent. Chemistry is rate limiting for the aldolase reaction, and two protons and a likely solvent contribution are involved in formation and breakage of a common intermediate
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
2-Amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
?
show the reaction diagram
-
first enzyme in the folate synthesis pathway
-
-
-
2-Amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
?
show the reaction diagram
-
first enzyme in the folate synthesis pathway
-
-
-
2-Amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
?
show the reaction diagram
-
enzyme is involved in the biosynthetic pathway of tetrahydrofolate
-
-
-
2-Amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
?
show the reaction diagram
-
the enzyme is involved in the de novo synthesis of folic acid from guanosine triphosphate
-
-
-
7,8-dihydroneopterin
6-hydroxymethyl-7,8-dihydropterin + glycolaldehyde
show the reaction diagram
-
-
-
-
?
7,8-dihydroneopterin
6-hydroxymethyl-7,8-dihydropterin + glycolaldehyde
show the reaction diagram
-
-
-
-
?
7,8-dihydroneopterin
6-hydroxymethyl-7,8-dihydropterin + glycolaldehyde
show the reaction diagram
Escherichia coli MG1655
-
-
-
-
?
additional information
?
-
-
enzyme in folate biosynthesis
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
P9WNC5
no metal required
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-Amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine
-
competitive
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-(1-hydroxycyclohexylmethyl)benzamide
-
IC50: 0.00074 mM
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-(2,2-bis-hydroxymethylbutyl)benzamide
-
IC50: 0.00095 mM
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-(2,3-dihydrobenzofuran-5-ylmethyl)benzamide
-
IC50: 0.00055 mM
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-(3,5-bistrifluoromethylbenzyl)benzamide
-
IC50: 0.001 mM
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-(3,5-dichlorobenzyl)benzamid
-
IC50: 0.000068 mM
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-(3-hydroxy-2,2-dimethylpropyl)benzamide
-
IC50: 0.00073 mM
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-(3-hydroxypropyl)benzamide
-
IC50: 0.0023 mM
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-(4-hydroxybutyl)benzamide
-
IC50: 0.002 mM
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-(4-phenoxybenzyl)benzamide
-
IC50: 0.022 mM
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-benzo[1,3]dioxol-5-ylmethylbenzamide
-
IC50: 0.00031 mM
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-biphenyl-4-ylmethylbenzamide
-
IC50: 0.025 mM
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-cis-(2-hydroxycycloheptylmethyl)benzamide
-
IC50: 0.00035 mM
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-cis-(2-hydroxycyclohexylmethyl)benzamide
-
IC50: 0.00041 mM
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-trans-(2-hydroxycyclohexylmethyl)benzamide
-
IC50: 0.00032 mM
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-[2-(2-hydroxymethylphenylsulfanyl)benzyl]-benzamide
-
IC50: 0.00003 mM
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)benzoic acid
-
IC50: 0.0015 mM
6-Formyl-dihydropterin
-
-
6-Methyl-dihydropterin
-
-
7,8-dihydrobiopterin
-
builds a complex with the enzyme
dihydrofolic acid
-
slight
dihydrofolic acid
-
-
Dihydropteroic acid
-
slight
monapterin
P56740
-
neopterin
P56740
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
EDTA
-
increases activity
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0023
2-amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
-
-
0.009
2-amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
-
-
0.021
2-amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
-
cleavage
0.043
2-amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
-
epimerization
0.045
2-amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
-
epimerization
0.064
2-amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine
-
cleavage
0.00076
7,8-dihydro-L-monapterin
-
mutant enzyme E21A, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
0.0029
7,8-dihydro-L-monapterin
-
mutant enzyme K98A, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
0.004
7,8-dihydro-L-monapterin
-
mutant enzyme E22A, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
0.0055
7,8-dihydro-L-monapterin
-
wild type enzyme, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
0.0095
7,8-dihydro-L-monapterin
-
mutant enzyme K100A, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
8
7,8-dihydro-L-monapterin
-
wild type enzyme, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
9.8
7,8-dihydro-L-monapterin
-
mutant enzyme E73A, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
0.00017
7,8-dihydromonapterin
P9WNC5
pH 7.0, 22C
0.016
7,8-dihydromonapterin
-
cleavage
0.019
7,8-dihydromonapterin
-
epimerization
0.036
7,8-dihydromonapterin
-
cleavage
0.057
7,8-dihydromonapterin
-
epimerization
0.00016
7,8-dihydroneopterin
P9WNC5
pH 7.0, 22C
0.0016
7,8-dihydroneopterin
-
mutant enzyme E21A, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
0.0024
7,8-dihydroneopterin
-
mutant enzyme K98A, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
0.0039
7,8-dihydroneopterin
-
mutant enzyme E22A, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
0.0046
7,8-dihydroneopterin
-
wild type enzyme, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
0.0058
7,8-dihydroneopterin
-
mutant enzyme K100A, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
0.0074
7,8-dihydroneopterin
-
wild type enzyme, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
9.7
7,8-dihydroneopterin
-
mutant enzyme E73A, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
10
glycoaldehyde
-
apparent value
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000023
7,8-dihydro-L-monapterin
-
mutant enzyme E21A, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
0.0000051
7,8-dihydro-L-monapterin
-
mutant enzyme K100A, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
0.0000053
7,8-dihydro-L-monapterin
-
mutant enzyme K98A, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
0.0000057
7,8-dihydro-L-monapterin
-
mutant enzyme K100Q, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
0.000006
7,8-dihydro-L-monapterin
-
mutant enzyme E73A, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
0.0000065
7,8-dihydro-L-monapterin
-
mutant enzyme E22A, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
0.01
7,8-dihydro-L-monapterin
-
wild type enzyme, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
0.089
7,8-dihydro-L-monapterin
-
wild type enzyme, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
0.006
7,8-dihydromonapterin
P9WNC5
pH 7.0, 22C
0.0000022
7,8-dihydroneopterin
-
mutant enzyme K100A, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
0.0000043
7,8-dihydroneopterin
-
mutant enzyme K98A, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
0.0000065
7,8-dihydroneopterin
-
mutant enzyme E21A, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
0.0000093
7,8-dihydroneopterin
-
mutant enzyme E22A, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
0.000016
7,8-dihydroneopterin
-
mutant enzyme K100Q, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
0.00073
7,8-dihydroneopterin
-
mutant enzyme E73A, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
0.0054
7,8-dihydroneopterin
P9WNC5
pH 7.0, 22C
0.045
7,8-dihydroneopterin
-
wild type enzyme, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
0.082
7,8-dihydroneopterin
-
wild type enzyme, in 100 mM Tris-HCl, 1 mM EDTA, and 5 mM dithiothreitol (pH 8.3)
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
38
7,8-dihydromonapterin
P9WNC5
pH 7.0, 22C
16051
36
7,8-dihydroneopterin
P9WNC5
pH 7.0, 22C
3544
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00074
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-(1-hydroxycyclohexylmethyl)benzamide
-
IC50: 0.00074 mM
0.00095
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-(2,2-bis-hydroxymethylbutyl)benzamide
-
IC50: 0.00095 mM
0.00055
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-(2,3-dihydrobenzofuran-5-ylmethyl)benzamide
-
IC50: 0.00055 mM
0.001
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-(3,5-bistrifluoromethylbenzyl)benzamide
-
IC50: 0.001 mM
0.000068
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-(3,5-dichlorobenzyl)benzamid
-
IC50: 0.000068 mM
0.00073
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-(3-hydroxy-2,2-dimethylpropyl)benzamide
-
IC50: 0.00073 mM
0.0023
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-(3-hydroxypropyl)benzamide
-
IC50: 0.0023 mM
0.002
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-(4-hydroxybutyl)benzamide
-
IC50: 0.002 mM
0.022
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-(4-phenoxybenzyl)benzamide
-
IC50: 0.022 mM
0.00031
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-benzo[1,3]dioxol-5-ylmethylbenzamide
-
IC50: 0.00031 mM
0.025
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-biphenyl-4-ylmethylbenzamide
-
IC50: 0.025 mM
0.00035
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-cis-(2-hydroxycycloheptylmethyl)benzamide
-
IC50: 0.00035 mM
0.00041
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-cis-(2-hydroxycyclohexylmethyl)benzamide
-
IC50: 0.00041 mM
0.00032
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-trans-(2-hydroxycyclohexylmethyl)benzamide
-
IC50: 0.00032 mM
0.00003
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-[2-(2-hydroxymethylphenylsulfanyl)benzyl]-benzamide
-
IC50: 0.00003 mM
0.0015
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)benzoic acid
-
IC50: 0.0015 mM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
62300
P9WNC5
apo-enzyme, mass spectrometry
727676
100000
-
gel filtration
5107
104000
-
equilibrium sedimentation
5109
110000
-
sedimentation equilibrium centrifugation
5110
119000
-
independent monofunctional activity FasAB-Met23, gel filtration
5106
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 100000, SDS-PAGE
octamer
-
8 * 13577, calculation from nucleotide sequence
octamer
-
8 * 12456, calculation from nucleotide sequence
octamer
-
8 * 13751, calculation from nucleotide sequence
octamer
-
x-ray crystallography
octamer
-
x-ray crystallography
octamer
-
8 * 14000, gel filtration
octamer
-
8 * 14600, gel filtration
tetramer
-
or trimer, 3 * or 4 * 31000, bifunctional enzyme with dihydroneopterin aldolase activity and hydroxymethyldihydropterin pyrophosphokinase activity, dihydroneopterin aldolase activity requires the multimeric protein, whereas pyrophosphokinase is expressed by the monomeric form, SDS-PAGE
tetramer
-
4 * 29689, independent monofunctional activity FasAB-Met23, mass spectrometry
tetramer
-
active enzyme in solution
tetramer
P9WNC5
apo-enzyme, 4 * 16585, and octamer for 7,8-dihydroxanthopterin-bound form, 8 * 16585, mass spectrometry
trimer
-
or tetramer, 4 * or 3 * 31000, bifunctional enzyme with dihydroneopterin aldolase activity and hydroxymethyldihydropterin pyrophosphokinase activity, dihydroneopterin aldolase activity requires the multimeric protein, whereas pyrophosphokinase is expressed by the monomeric form, SDS-PAGE
?
-
x * 83979, multifunctional Fas enzyme with the activity of the first three enzymes of the folate synthesis pathway: dihydroneopterin aldolase, hydroxymethyldihydropterin pyrophosphokinase and dihydropteroate synthase, calculation from nucleotide sequence, x * 71500, Fas multifunctional enzyme with the activity of the first three enzymes of the folate synthesis pathway: dihydroneopterin aldolase, hydroxymethyldihydropterin pyrophosphokinase and dihydropteroate synthase, SDS-PAGE
additional information
-
four molecules assemble into a ring, and two rings come together to give a cylinder with a hole of at least 13 A diameter
additional information
-
FasA and FasB may be two subunits of the dihydroneopterin aldolase enzyme moiety within the multifunctional Fas protein
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
sitting-drop vapour-diffusion method by mixing 2 ml of a solution containing 11.5 mg of protein per ml with an equal volume of reservoir solution containing 0.1 M Tris hydrochloride (pH 7.2), 21% polyethylene glycol (PEG 2000 MME), and 115 mM cyclohexyl-butanoyl-N-hydroxyethylglucamide. Diffraction data are collected to a resolution of 2.2 A. The crystals belonged to space group P1 with the unit cell constants a = 63.5 A, b = 84.2 A, c = 89.1 A, alpha = 90.14, beta = 89.9, gamma = 76.2, and has a solvent content of 42%
Q9SF23
hanging drop vapour diffusion method, co-crystallization with monapterin or neopterin, in 1.4 M sodium acetate, 0.2 M imidazole, 0.1 M sodium cacodylate (pH 6.5), at 19C
P56740
hanging drop vapour diffusion method with 50 mM MOPS/NaOH (pH 7.0), 17.5% (w/v) methoxy-PEG 2000, 400 mM NaCl, 10 mM MgCl2, 2 mM dithiothreitol, 1 mM EDTA and 5% (v/v) glycerol
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
100
-
5 min, stable
5104
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
DEAE-cellulose column chromatography and Bio-Gel A-0.5m gel filtration
-
Ni-nitrilotriacetate column chromatography, DEAE-cellulose column chromatography and Bio-Gel A-0.5 m gel filtration
-
native and recombinant independent monofunctional activity FasAB-Met23
-
DEAE-cellulose column chromatography and Bio-Gel A 0.5 m gel filtration
P56740
Ni-nitrilotriacetate column chromatography, DEAE-cellulose column chromatography and Bio-Gel A-0.5 m gel filtration
-
Ni-NTA column chromatography and Bio-Gel A-0.5m gel filtration
-
Mono Q 10/10 column chromatography, Superdex 200 gel filtration
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli
-
expressed in Escherichia coli BL21(DE3) cells
-
expressed in Escherichia coli folB deletant cells
-
expression in Escherichia coli
-
overexpression of the multifunctional Fas enzyme with the activity of the first three enzymes of the folate synthesis pathway: dihydroneopterin aldolase, hydroxymethyldihydropterin pyrophosphokinase and dihydropteroate synthase in cultured Spodoptera frugiperda insect cells
-
overproduced as an independent monofunctional activity in Escherichia coli, FasAB-Met23
-
expressed in Escherichia coli
-
expressed in Escherichia coli BL21(DE3) cells
-
expressed in Escherichia coli BL21 (DE3) cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
DHNA expression is significantly elevated only in fruit overexpressing GCHI (and accumulating pterins)
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E21A
-
strongly reduced kcat
E73A
-
strongly reduced kcat
K98A
-
strongly reduced kcat
Y53F
-
the mutation converts the enzyme to a cofactor-independent oxygenase, which generates mainly 7,8-dihydroxanthopterin
D39E
-
FasA domain mutant D39E and FasB domain mutant G175A have no detectable activity of dihydroneopterin aldolase. The FasA domain mutants, G53A and Q63N and the FasB domain mutant Q185N, show approximately 11-fold, 16-fold and 24-fold decrease, respectively, in specific activity compared to wild-type FasAB-Met23. The activity of the FasB domain mutant D161E is similar to that of wild-type enzyme. The two mutant enzymes K96R and K218R have levels of activity comparable to wild-type enzyme
G175A
-
FasA domain mutant D39E and FasB domain mutant G175A have no detectable activity of dihydroneopterin aldolase. The FasA domain mutants, G53A and Q63N and the FasB domain mutant Q185N, show approximately 11-fold, 16-fold and 24-fold decrease, respectively, in specific activity compared to wild-type FasAB-Met23. The activity of the FasB domain mutant D161E is similar to that of wild-type enzyme. The two mutant enzymes K96R and K218R have levels of activity comparable to wild-type enzyme
E22A
-
strongly reduced kcat
E29A
-
multistage tandem mass spectrometry (MS/MS and MS3) of gas-phase fragmentation reaction of the mutant enzyme yields identical product ion spectrum to the wild-type protein
E74A
-
mutation causes dramatic changes in the affinities of the enzyme for the substrate or product analogues or the rate constants
E81A
-
multistage tandem mass spectrometry (MS/MS and MS3) of gas-phase fragmentation reaction of the mutant enzyme yields identical product ion spectrum to the wild-type protein
K100A
-
strongly reduced kcat
K100Q
-
strongly reduced kcat
K107A
-
multistage tandem mass spectrometry (MS/MS and MS3) of gas-phase fragmentation reaction of the mutant enzyme is compared to that of wild-type enzyme It yields significantly different product ion spectra dominated by cleaves occuring N-terminal to Pro
Y54F
-
the mutation converts the enzyme to a cofactor-independent oxygenase, which generates mainly 7,8-dihydroxanthopterin
Y61F
-
multistage tandem mass spectrometry (MS/MS and MS3) of gas-phase fragmentation reaction of the mutant enzyme yields identical product ion spectrum to the wild-type protein
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
drugs targeting folate metabolism have long been used as highly successful antimicrobial and anticancer agents
pharmacology
-
the Fas multifunctional enzyme with the activity of the first three enzymes of the folate synthesis pathway: dihydroneopterin aldolase, hydroxymethyldihydropterin pyrophosphokinase and dihydropteroate synthase is an attractive target for chemotherapy, sin