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 ACCESSION NO.
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
-
-
-
-
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
-
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
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
elimination
-
-
of an aldehyde, C-C bond cleavage
-
PATHWAY
KEGG Link
MetaCyc Link
6-hydroxymethyl-dihydropterin diphosphate biosynthesis I
-
6-hydroxymethyl-dihydropterin diphosphate biosynthesis II (archaea)
-
Folate biosynthesis
-
Metabolic pathways
-
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 ACCESSION NO.
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
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
37290-59-8
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
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 ACCESSION NO.
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
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
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
-
-
-
-
?
7,8-dihydro-L-monapterin
?
show the reaction diagram
-
-
-
-
?
7,8-Dihydromonapterin
?
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
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
-
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
-
?
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
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
-
?
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
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
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
EDTA
-
increases activity
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
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)
0.016
-
7,8-dihydromonapterin
-
cleavage
0.019
-
7,8-dihydromonapterin
-
epimerization
0.036
-
7,8-dihydromonapterin
-
cleavage
0.057
-
7,8-dihydromonapterin
-
epimerization
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]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
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)
0.0000022
-
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)
0.045
-
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)
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
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]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.0039
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
100000
-
-
gel filtration
104000
-
-
equilibrium sedimentation
110000
-
-
sedimentation equilibrium centrifugation
119000
-
-
independent monofunctional activity FasAB-Met23, gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 100000, SDS-PAGE
octamer
-
8 * 12456, calculation from nucleotide sequence
octamer
-
8 * 13577, calculation from nucleotide sequence
octamer
-
8 * 13751, calculation from nucleotide sequence
octamer
-
8 * 14000, gel filtration
octamer
-
8 * 14600, gel filtration
octamer
-
x-ray crystallography
octamer
-
x-ray crystallography
tetramer
-
4 * 29689, independent monofunctional activity FasAB-Met23, mass spectrometry
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
-
active enzyme in solution
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 * 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; 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
additional information
-
FasA and FasB may be two subunits of the dihydroneopterin aldolase enzyme moiety within the multifunctional Fas protein
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
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
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 19°C
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
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
100
-
-
5 min, stable
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
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 ACCESSION NO.
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 ACCESSION NO.
LITERATURE
DHNA expression is significantly elevated only in fruit overexpressing GCHI (and accumulating pterins)
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
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 ACCESSION NO.
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