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Information on EC 4.1.2.25 - dihydroneopterin aldolase and Organism(s) Staphylococcus aureus and UniProt Accession P56740

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EC Tree
     4 Lyases
         4.1 Carbon-carbon lyases
             4.1.2 Aldehyde-lyases
                4.1.2.25 dihydroneopterin aldolase
IUBMB Comments
The enzyme participates in folate (in bacteria, plants and fungi) and methanopterin (in archaea) biosynthesis. The enzymes from the bacterium Escherichia coli and the plant Arabidopsis thaliana also catalyse the epimerisation of the 2' hydroxy-group (EC 5.1.99.8, 7,8-dihydroneopterin epimerase) [2,3]. The enzyme from the bacterium Mycobacterium tuberculosis is trifunctional and also catalyses EC 5.1.99.8 and EC 1.13.11.81, 7,8-dihydroneopterin oxygenase . The enzyme from the yeast Saccharomyces cerevisiae also catalyses the two subsequent steps in the folate biosynthesis pathway - EC 2.7.6.3, 2-amino-4-hydroxy-6-(hydroxymethyl)dihydropteridine diphosphokinase, and EC 2.5.1.15, dihydropteroate synthase .
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Staphylococcus aureus
UNIPROT: P56740
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The taxonomic range for the selected organisms is: Staphylococcus aureus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
dihydroneopterin aldolase, dhna-hppk, rv3607c, dihydroneopterin aldolase/epimerase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
aldolase, dihydroneopterin
-
-
-
-
FASA
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
7,8-dihydroneopterin = 6-(hydroxymethyl)-7,8-dihydropterin + glycolaldehyde
show the reaction diagram
mechanism
-
PATHWAY SOURCE
PATHWAYS
-
-, -, -, -
SYSTEMATIC NAME
IUBMB Comments
7,8-dihydroneopterin glycolaldehyde-lyase [6-(hydroxymethyl)-7,8-dihydropterin-forming]
The enzyme participates in folate (in bacteria, plants and fungi) and methanopterin (in archaea) biosynthesis. The enzymes from the bacterium Escherichia coli and the plant Arabidopsis thaliana also catalyse the epimerisation of the 2' hydroxy-group (EC 5.1.99.8, 7,8-dihydroneopterin epimerase) [2,3]. The enzyme from the bacterium Mycobacterium tuberculosis is trifunctional and also catalyses EC 5.1.99.8 and EC 1.13.11.81, 7,8-dihydroneopterin oxygenase [6]. The enzyme from the yeast Saccharomyces cerevisiae also catalyses the two subsequent steps in the folate biosynthesis pathway - EC 2.7.6.3, 2-amino-4-hydroxy-6-(hydroxymethyl)dihydropteridine diphosphokinase, and EC 2.5.1.15, dihydropteroate synthase [4].
CAS REGISTRY NUMBER
COMMENTARY hide
37290-59-8
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
7,8-dihydroneopterin
6-hydroxymethyl-7,8-dihydropterin + 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
?
show the reaction diagram
-
the enzyme is involved in the de novo synthesis of folic acid from guanosine triphosphate
-
-
?
6-hydroxymethyl-7,8-dihydropterin
?
show the reaction diagram
-
-
-
-
?
7,8-dihydro-L-monapterin
?
show the reaction diagram
-
-
-
-
?
7,8-dihydroneopterin
6-hydroxymethyl-7,8-dihydropterin + glycolaldehyde
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
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
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
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
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.004 - 0.0095
7,8-dihydro-L-monapterin
0.0039 - 0.0058
7,8-dihydroneopterin
10
glycoaldehyde
-
apparent value
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0000051 - 0.01
7,8-dihydro-L-monapterin
0.0000022 - 0.045
7,8-dihydroneopterin
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00074
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-(1-hydroxycyclohexylmethyl)benzamide
Staphylococcus aureus
-
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
Staphylococcus aureus
-
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
Staphylococcus aureus
-
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
Staphylococcus aureus
-
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
Staphylococcus aureus
-
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
Staphylococcus aureus
-
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
Staphylococcus aureus
-
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
Staphylococcus aureus
-
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
Staphylococcus aureus
-
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
Staphylococcus aureus
-
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
Staphylococcus aureus
-
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
Staphylococcus aureus
-
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
Staphylococcus aureus
-
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
Staphylococcus aureus
-
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
Staphylococcus aureus
-
IC50: 0.00003 mM
0.0015
3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)benzoic acid
Staphylococcus aureus
-
IC50: 0.0015 mM
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
FOLB_STAAU
121
0
13751
Swiss-Prot
-
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
110000
-
sedimentation equilibrium centrifugation
13751
-
8 * 13751, calculation from nucleotide sequence
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
octamer
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
LITERATURE
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
in complex with neopterin, an analog of dihydroneoptierin, and with monapterin, to 1.7 A and 1.68 A resolution, respectively. Active site residues E22, K100, and Y54 function coordinately during catalysis
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
DEAE-cellulose column chromatography and Bio-Gel A 0.5 m gel filtration
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
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
expressed in Escherichia coli BL21(DE3) cells
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hennig, M.; D'Arcy, A.; Hampele, I.C.; Page, M.G.P.; Oefner, C.; Dale, G.E.
Crystal structure and reaction mechanism of 7,8-dihydroneopterin aldolase from Staphylococcus aureus
Nat. Struct. Biol.
5
357-362
1998
Staphylococcus aureus
Manually annotated by BRENDA team
Scherperel, G.; Yan, H.; Wang, Y.; Reid, G.E.
'Top-down' characterization of site-directed mutagenesis products of Staphylococcus aureus dihydroneopterin aldolase by multistage tandem mass spectrometry in a linear quadrupole ion trap
Analyst
131
291-302
2006
Staphylococcus aureus
Manually annotated by BRENDA team
Sanders, W.J.; Nienaber, V.L.; Lerner, C.G.; McCall, J.O.; Merrick, S.M.; Swanson, S.J.; Harlan, J.E.; Stoll, V.S.; Stamper, G.F.; Betz, S.F.; Condroski, K.R.; Meadows, R.P.; Severin, J.M.; Walter, K.A.; Magdalinos, P.; Jakob, C.G.; Wagner, R.; Beutel, B.A.
Discovery of potent inhibitors of dihydroneopterin aldolase using CrystaLEAD high-throughput X-ray crystallographic screening and structure-directed lead optimization
J. Med. Chem.
47
1709-1718
2004
Staphylococcus aureus
Manually annotated by BRENDA team
Wang, Y.; Li, Y.; Yan, H.
Mechanism of dihydroneopterin aldolase: functional roles of the conserved active site glutamate and lysine residues
Biochemistry
45
15232-15239
2006
Escherichia coli, Staphylococcus aureus
Manually annotated by BRENDA team
Wang, Y.; Li, Y.; Wu, Y.; Yan, H.
Mechanism of dihydroneopterin aldolase. NMR, equilibrium and transient kinetic studies of the Staphylococcus aureus and Escherichia coli enzymes
FEBS J.
274
2240-2252
2007
Escherichia coli, Staphylococcus aureus
Manually annotated by BRENDA team
Wang, Y.; Scherperel, G.; Roberts, K.D.; Jones, A.D.; Reid, G.E.; Yan, H.
A point mutation converts dihydroneopterin aldolase to a cofactor-independent oxygenase
J. Am. Chem. Soc.
128
13216-13223
2006
Escherichia coli, Staphylococcus aureus
Manually annotated by BRENDA team
Blaszczyk, J.; Li, Y.; Gan, J.; Yan, H.; Ji, X.
Structural basis for the aldolase and epimerase activities of Staphylococcus aureus dihydroneopterin aldolase
J. Mol. Biol.
368
161-169
2007
Staphylococcus aureus (P56740), Staphylococcus aureus
Manually annotated by BRENDA team
Yao, L.; Yan, H.; Cukier, R.I.
Mechanism of dihydroneopterin aldolase: a molecular dynamics study of the apo enzyme and its product complex
J. Phys. Chem. B
110
1443-1456
2006
Staphylococcus aureus
Manually annotated by BRENDA team