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Information on EC 3.1.3.46 - fructose-2,6-bisphosphate 2-phosphatase and Organism(s) Homo sapiens and UniProt Accession O60825

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EC Tree
     3 Hydrolases
         3.1 Acting on ester bonds
             3.1.3 Phosphoric-monoester hydrolases
                3.1.3.46 fructose-2,6-bisphosphate 2-phosphatase
IUBMB Comments
The enzyme copurifies with EC 2.7.1.105 6-phosphofructo-2-kinase. (cf. EC 3.1.3.54 fructose-2,6-bisphosphate 6-phosphatase).
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This record set is specific for:
Homo sapiens
UNIPROT: O60825
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The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
fbpase, pfkfb3, tigar, pfk-2, pfkfb4, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, fructose-2,6-bisphosphatase, pfkfb2, pfk-2/fbpase-2, f-2,6-p2, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
-
fructose-2,6-bisphosphatase
-
heart 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
-
PFK-2/FBPase-2
-
6-phosphofructo-2-kinase/2,6-bisphosphatase 3
-
-
6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase
-
-
6-phosphofructo-2-kinase/fructose-2 6-biphosphatase
-
-
6-phosphofructo-2-kinase/fructose-2,6-bisphosphase
-
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (gene PFKFB3)
-
bifunctional enzyme
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2
-
-
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4
-
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-4
6PF2K/Fru-2,6-P2ase
-
-
D-fructose-2,6-bisphosphatase
-
-
-
-
FBPase-2
fructose-2,6-bisphosphatase
fructose-2,6-diphosphatase
-
-
-
-
Pfk-2
-
-
PFK-2/FBPase
-
-
PFK-2/FBPase-2
PFK-2/FDPase-2
-
-
PFKFB
PFKFB3
PFKFB4
phosphatase, fructose 2,6-di-
-
-
-
-
additional information
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
beta-D-fructose 2,6-bisphosphate + H2O = D-fructose 6-phosphate + phosphate
show the reaction diagram
FBPase performs a reaction following a classical ping pong mechanism with formation of a phosphoryl-enzyme intermediate on a histidine residue located in an Arg-His-Gly triad, catalytic site structure, overview
beta-D-fructose 2,6-bisphosphate + H2O = D-fructose 6-phosphate + phosphate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of phosphoric ester
PATHWAY SOURCE
PATHWAYS
-
-
SYSTEMATIC NAME
IUBMB Comments
beta-D-fructose-2,6-bisphosphate 2-phosphohydrolase
The enzyme copurifies with EC 2.7.1.105 6-phosphofructo-2-kinase. (cf. EC 3.1.3.54 fructose-2,6-bisphosphate 6-phosphatase).
CAS REGISTRY NUMBER
COMMENTARY hide
81611-75-8
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
beta-D-fructose 2,6-bisphosphate + H2O
D-fructose 6-phosphate + phosphate
show the reaction diagram
beta-D-fructose 2,6-bisphosphate + H2O
D-fructose 6-phosphate + phosphate
show the reaction diagram
D-fructose 2,6-bisphosphate + H2O
D-fructose 6-phosphate + phosphate
show the reaction diagram
-
-
-
-
?
fructose 2,6-bisphosphate + H2O
?
show the reaction diagram
-
-
-
-
?
fructose 2,6-bisphosphate + H2O
fructose 6-phosphate + phosphate
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
beta-D-fructose 2,6-bisphosphate + H2O
D-fructose 6-phosphate + phosphate
show the reaction diagram
beta-D-fructose 2,6-bisphosphate + H2O
D-fructose 6-phosphate + phosphate
show the reaction diagram
D-fructose 2,6-bisphosphate + H2O
D-fructose 6-phosphate + phosphate
show the reaction diagram
-
-
-
-
?
fructose 2,6-bisphosphate + H2O
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2E)-2-(1,3-benzodioxol-5-ylmethylidene)butanedioic acid
-
mimics binding pattern of fructose 6-phosphate
([2-[(5-nitropyridin-2-yl)amino]phenyl]sulfanyl)acetic acid
-
mimics binding pattern of fructose 6-phosphate
1,1'-ethane-1,2-diylbis(4-acetylpyrrolidine-2,3,5-trione)
-
mimics binding pattern of fructose 6-phosphate
1-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-(2-methyl-4-nitro-1H-imidazol-1-yl)ethanol
-
mimics binding pattern of fructose 6-phosphate
1-(3-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one
-
1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one
-
1-amino-4-(2-nitro-1H-imidazol-1-yl)butan-2-ol
-
mimics binding pattern of fructose 6-phosphate
2-((5-bromo-6-oxo-1-phenyl-1,6-dihydropyridazin-4-yl)amino)acetamide
-
-
2-(1,3-benzodioxol-5-ylmethyl)-3-methylbutanedioic acid
-
mimics binding pattern of fructose 6-phosphate
2-(2-nitrophenoxy)-N-phenylacetamide
-
mimics binding pattern of fructose 6-phosphate
2-(3H-indol-7-ylmethyl)butanedioic acid
-
mimics binding pattern of fructose 6-phosphate
2-(5-amino-4-carbamoyl-1H-pyrazol-1-yl)ethanesulfonic acid
-
mimics binding pattern of fructose 6-phosphate
2-(5-bromo-6-oxo-1-phenyl-1,6-dihydropyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline-5-carbonitrile
-
-
2-(acetylamino)-beta-oxophenylalanine
-
mimics binding pattern of fructose 6-phosphate
2-nitro-N-(pyrazin-2-ylmethyl)benzenesulfonamide
-
mimics binding pattern of fructose 6-phosphate
2-nitro-N-quinolin-3-ylbenzenesulfonamide
-
mimics binding pattern of fructose 6-phosphate
2-[(4-nitro-1H-benzimidazol-7-yl)sulfanyl]ethyl benzoate
-
mimics binding pattern of fructose 6-phosphate
2-[(5-nitropyridin-2-yl)amino]ethyl 5-nitro-1H-pyrrole-2-carboxylate
-
mimics binding pattern of fructose 6-phosphate
2-[(furan-2-ylmethyl)amino]-5-nitrobenzoic acid
-
mimics binding pattern of fructose 6-phosphate
2-[[(2Z)-2-(phenylhydrazono)acetyl]amino]benzoic acid
-
mimics binding pattern of fructose 6-phosphate
2-[[2-(2,4-dinitrophenyl)hydrazino]carbonyl]benzoic acid
-
mimics binding pattern of fructose 6-phosphate
3,3'-(2,4,6-trioxo-1,3,5-triazinane-1,3-diyl)dipropanoic acid
-
mimics binding pattern of fructose 6-phosphate
3-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)-N-(tetrahydrofuran-2-ylmethyl)propanamide
-
mimics binding pattern of fructose 6-phosphate
3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one
-
-
3-acetylphenyl (3-acetylphenyl)acetate
-
mimics binding pattern of fructose 6-phosphate
3-[(2-pyridin-2-ylhydrazino)carbonyl]pyrazine-2-carboxylic acid
-
mimics binding pattern of fructose 6-phosphate
4-(4-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-5-bromo-6-oxopyridazin-1(6H)-yl)benzonitrile
-
-
4-bromo-2-phenyl-5-(((tetrahydrofuran-2-yl)methyl)amino)pyridazin-3(2H)-one
-
-
4-bromo-2-phenyl-5-(2-oxa-6-azaspiro[3.3]heptan-6-yl)pyridazin-3(2H)-one
-
-
4-bromo-5-morpholino-2-phenylpyridazin-3(2H)-one
-
-
5,6,7,8-tetrahydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one
-
competitive inhibitor
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-2-benzyl-4-bromopyridazin-3(2H)-one
-
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-2-benzylpyridazin-3(2H)-one
-
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(3-phenylpropyl)pyridazin-3(2H)-one
-
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(4-((2-(dimethylamino)ethyl)-amino)benzyl)pyridazin-3(2H)-one
-
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(4-(trifluoromethoxy)phenyl)-pyridazin-3(2H)-one
-
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(4-chlorophenyl)pyridazin-3(2H)-one
-
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(4-iodobenzyl)pyridazin-3(2H)-one
-
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(pyrimidin-5-yl)pyridazin-3(2H)-one
-
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-phenethylpyridazin-3(2H)-one
-
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-phenylpyridazin-3(2H)-one
-
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-chloro-2-phenylpyridazin-3(2H)-one
-
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-ethoxy-2-phenylpyridazin-3(2H)-one
-
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-iodo-2-phenylpyridazin-3(2H)-one
-
-
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-isopropyl-2-phenylpyridazin-3(2H)-one
-
-
5-hydroxy-N-(4-nitro-1,3-thiazol-2-yl)-2,4-dioxopentanamide
-
mimics binding pattern of fructose 6-phosphate
citrate
-
inhibits the cardiac enzyme
dimethyloxalylglycine
inhibits the splice isozyme PFKFB-4
ethyl 1-(6-oxo-1-phenyl-5-(2-oxa-6-azaspiro[3.3]heptan-6-yl)-1,6-dihydropyridazin-4-yl)-1H-1,2,3-triazole-4-carboxylate
-
-
fructose 6-phosphate
-
noncompetetive
phosphoenolpyruvate
-
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Cyclic AMP dependent protein kinase
-
-
-
Protein kinase C
-
-
-
additional information
-
the hepatic enzyme expression is stimulated at transcriptional level by both insulin and glucocorticoids
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0102 - 0.204
beta-D-fructose 2,6-bisphosphate
0.0043 - 0.016
fructose 2,6-bisphosphate
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1
2-((5-bromo-6-oxo-1-phenyl-1,6-dihydropyridazin-4-yl)amino)acetamide
Homo sapiens
-
IC50 above 1.0 mM, in 40 mM Tris pH 7.5, 20 mM MgCl2, 0.1 mg/ml bovine serum albumin, at 30°C
0.5
2-(5-bromo-6-oxo-1-phenyl-1,6-dihydropyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline-5-carbonitrile
Homo sapiens
-
IC50 above 0.5 mM,in 40 mM Tris pH 7.5, 20 mM MgCl2, 0.1 mg/ml bovine serum albumin, at 30°C
0.026
3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one
Homo sapiens
-
in 40 mM Tris pH 7.5, 20 mM MgCl2, 0.1 mg/ml bovine serum albumin, at 30°C
0.0084
4-(4-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-5-bromo-6-oxopyridazin-1(6H)-yl)benzonitrile
Homo sapiens
-
in 40 mM Tris pH 7.5, 20 mM MgCl2, 0.1 mg/ml bovine serum albumin, at 30°C
1
4-bromo-2-phenyl-5-(((tetrahydrofuran-2-yl)methyl)amino)pyridazin-3(2H)-one
Homo sapiens
-
IC50 above 1.0 mM, in 40 mM Tris pH 7.5, 20 mM MgCl2, 0.1 mg/ml bovine serum albumin, at 30°C
1
4-bromo-2-phenyl-5-(2-oxa-6-azaspiro[3.3]heptan-6-yl)pyridazin-3(2H)-one
Homo sapiens
-
IC50 above 1.0 mM, in 40 mM Tris pH 7.5, 20 mM MgCl2, 0.1 mg/ml bovine serum albumin, at 30°C
1
4-bromo-5-morpholino-2-phenylpyridazin-3(2H)-one
Homo sapiens
-
IC50 above 1.0 mM,in 40 mM Tris pH 7.5, 20 mM MgCl2, 0.1 mg/ml bovine serum albumin, at 30°C
0.0034
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-2-benzyl-4-bromopyridazin-3(2H)-one
Homo sapiens
-
in 40 mM Tris pH 7.5, 20 mM MgCl2, 0.1 mg/ml bovine serum albumin, at 30°C
10
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-2-benzylpyridazin-3(2H)-one
Homo sapiens
-
IC50 above 10 mM, in 40 mM Tris pH 7.5, 20 mM MgCl2, 0.1 mg/ml bovine serum albumin, at 30°C
0.011
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(3-phenylpropyl)pyridazin-3(2H)-one
Homo sapiens
-
in 40 mM Tris pH 7.5, 20 mM MgCl2, 0.1 mg/ml bovine serum albumin, at 30°C
0.5
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(4-((2-(dimethylamino)ethyl)-amino)benzyl)pyridazin-3(2H)-one
Homo sapiens
-
IC50 above 0.5 mM, in 40 mM Tris pH 7.5, 20 mM MgCl2, 0.1 mg/ml bovine serum albumin, at 30°C
0.0091
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(4-(trifluoromethoxy)phenyl)-pyridazin-3(2H)-one
Homo sapiens
-
in 40 mM Tris pH 7.5, 20 mM MgCl2, 0.1 mg/ml bovine serum albumin, at 30°C
0.007
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(4-chlorophenyl)pyridazin-3(2H)-one
Homo sapiens
-
in 40 mM Tris pH 7.5, 20 mM MgCl2, 0.1 mg/ml bovine serum albumin, at 30°C
0.0087
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(4-iodobenzyl)pyridazin-3(2H)-one
Homo sapiens
-
in 40 mM Tris pH 7.5, 20 mM MgCl2, 0.1 mg/ml bovine serum albumin, at 30°C
0.0096
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(pyrimidin-5-yl)pyridazin-3(2H)-one
Homo sapiens
-
in 40 mM Tris pH 7.5, 20 mM MgCl2, 0.1 mg/ml bovine serum albumin, at 30°C
0.0026
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-phenethylpyridazin-3(2H)-one
Homo sapiens
-
in 40 mM Tris pH 7.5, 20 mM MgCl2, 0.1 mg/ml bovine serum albumin, at 30°C
0.0074
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-phenylpyridazin-3(2H)-one
Homo sapiens
-
in 40 mM Tris pH 7.5, 20 mM MgCl2, 0.1 mg/ml bovine serum albumin, at 30°C
0.0262
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-chloro-2-phenylpyridazin-3(2H)-one
Homo sapiens
-
in 40 mM Tris pH 7.5, 20 mM MgCl2, 0.1 mg/ml bovine serum albumin, at 30°C
1
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-ethoxy-2-phenylpyridazin-3(2H)-one
Homo sapiens
-
IC50 above 1.0 mM, in 40 mM Tris pH 7.5, 20 mM MgCl2, 0.1 mg/ml bovine serum albumin, at 30°C
0.013
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-iodo-2-phenylpyridazin-3(2H)-one
Homo sapiens
-
in 40 mM Tris pH 7.5, 20 mM MgCl2, 0.1 mg/ml bovine serum albumin, at 30°C
0.5
5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-isopropyl-2-phenylpyridazin-3(2H)-one
Homo sapiens
-
IC50 above 0.5 mM, in 40 mM Tris pH 7.5, 20 mM MgCl2, 0.1 mg/ml bovine serum albumin, at 30°C
0.055
ethyl 1-(6-oxo-1-phenyl-5-(2-oxa-6-azaspiro[3.3]heptan-6-yl)-1,6-dihydropyridazin-4-yl)-1H-1,2,3-triazole-4-carboxylate
Homo sapiens
-
in 40 mM Tris pH 7.5, 20 mM MgCl2, 0.1 mg/ml bovine serum albumin, at 30°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
inducible expression of isozyme PFKFB3, visceral fat cell
Manually annotated by BRENDA team
-
overexpression of isozyme PFKFB-4 in breast and colon malignant tumors compared to non-malignant tissue, overexpression of isozyme PFKFB-4 is correlated with enhanced expression of isozyme PFKFB-3, hypoxia-inducible factor 1alpha, dependent glucose transporter 1, and vascular endothelial growth factor VEGF, overview
Manually annotated by BRENDA team
-
overexpression of isozyme PFKFB-4 in breast and colon malignant tumors compared to non-malignant tissue, overexpression of isozyme PFKFB-4 is correlated with enhanced expression of isozyme PFKFB-3, hypoxia-inducible factor 1alpha, dependent glucose transporter 1, and vascular endothelial growth factor VEGF, overview
Manually annotated by BRENDA team
melanoma cell line, minor splice isozyme PFKFB-4, major isozyme is PFKFB-3, isozyme PFKFB-4 is overexpressed in hypoxic conditions
Manually annotated by BRENDA team
minor splice isozyme PFKFB-4, major isozyme is PFKFB-3
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
knockdown of isoform PFKFB4 reduces tumor growth, glucose uptake and beta-D-fructose 2,6-bisphosphate and increases apoptosis
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
F262_HUMAN
505
0
58477
Swiss-Prot
other Location (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
12000
-
gel filtration
54000
-
x * 54000, there are 2 isoforms of 54000 and 58000 Da, SDS-PAGE
58000
-
x * 58000, there are 2 isoforms of 54000 and 58000 Da, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
homodimeric bifunctional enzyme
dimer
monomer
-
1* 36600 and 1* 35600 which seems a degradation product of the larger subunit, SDS-PAGE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
Akt phosphorylates the enzyme at Ser-483
phosphoprotein
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
to 2.0 A resolution. Citrate cocrystallizes in the 2-kinase domain, occupying the fructose-6-phosphate binding-site and extending into the gamma-phosphate binding pocket of ATP. In complex with ATP analogue AMPPNP, the presence of a gamma-phosphate makes adoption of the catalytic ATP binding mode impossible for AMPPNP, forcing the analogue to bind atypically with concomitant conformational changes to the ATP binding-pocket
by the sitting-drop, vapor-diffusion method, crystals of PFKFB D-fructose 6-phosphate complex in the presence of the nonreactive ATP-analogue AMPPCP beta,gamma-methyleneadenosine 5’-triphosphate and crystals the inhibitory complex of PFKFB ADP and phosphoenolpyruvate
-
crystal structure of the liver enzyme
-
in complex with D-fructose 6-phosphate, diphosphate, or AlF4, sitting drop vapor diffusion method, using 100 mM Tris-HCl, pH 7.5, 20-25% (w/v) ethylene glycol, 200-400 mM tartaric acid, 5% (v/v) glycerol, and 12% (w/v) polyethylene glycol 4000
purified recombinant inducible isozyme PFKFB3, 8 mg/ml protein in 20 mM Tris-HCl, pH 8.0, 10 mM sodium phosphate, 0.05 mM EDTA, 5 mM 2-mercaptoethanol, 0.2 mM ADP, 5% glycerol, and 0.2 mM fructose-6-phosphate, sitting drop vapour diffusion method in presence or absence of fructose-2,6-bisphosphate, the protein sample is mixed with an equal volume of mother liquor containing 50 mM Tris-HCl, pH 7.5, 20-25% ethylene glycol, 12% dioxane, 5% glycerol, and 12% PEG 4000, 2-3 weeks, removal of free phosphate from crystals prior to X-ray diffraction structure determination and analysis at 2.1 A resolution
sitting-drop vapor diffusion of the 1:1 mixture of the protein sample with mother liquor of 50 mM Tris-HCl, pH 7.5, 20.35% ethylene glycol, 12% dioxane, 5% glycerol, and 12% polyethylene glycol 4000. Crystals in a size of 0.2 * 0.2 * 0.05 mm grow in 2-3 weeks. Determination of structure at 2.1 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A44G
-
site directed mutagenesis
A44V
-
site directed mutagenesis
K168A
-
site directed mutagenesis
K168N
-
site directed mutagenesis
K168R
-
site directed mutagenesis
K472/473A
mutant fails to localize in nucleus, mainly localizes in cytoplasm. The mutant inhibits the autophagic process, stimulates lactate production, and decreases the activity of AMPK compared to the wild-type
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
glutathione Sepharose 4 column chromatography
-
Ni-NTA affinity column chromatography
recombinant His-tagged inducible isozyme PFKFB3 from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, after which the tag is cleaved off by thrombin, followed by anion exchange chromatography, to homogeneity
recombinant His6-tagged bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase from Escherichia coli strain BL21(DE3) pLysS by nickel affinity chromatography and anion exchange chromatography with triethylammonium bicarbonate as eluant
-
using Ni-NTA affinity columns
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
genes PFKFB1-4, chromosomal localization of tissue-specific isozymes, phylogenetic analysis, overview, transcriptional control of isozymes, overview
expressed in Escherichia coli BL21(DE3) cells
expression in Escherichia coli
-
expression of His-tagged inducible isozyme PFKFB3 in Escherichia coli strain BL21(DE3)
expression of His6-tagged bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in Escherichia coli strain BL21(DE3) pLysS
-
gene PFKFB4, DNA and amino acid sequence determination, expression analysis in DB-1 melanoma cells
genes PFKFB1-4, chromosomal localization of tissue-specific isozymes, phylogenetic analysis, overview, transcriptional control of isozymes, overview
KDO-phosphatase knockout, enzyme is encoded by 4 genes, PFKFB1-4, PFKFB3 is activated by mitogenic, inflammatory and hypoxic stimuli
-
overexpression in Escherichia coli as His6-tagged fusion protein
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
androgen stimulates glycolysis for de novo lipid synthesis by increasing the activities of hexokinase 2 and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2, up-regulation of PFKFB2 expression in LNCaP cells is mediated by the direct binding of ligand-activated androgen receptor to the PFKFB2 promoter. Expression of PFKFB2 gene is increased 3.0fold by treatment with methyltrienolone, i.e. R1881, a synthetic androgen
-
p53 downregulates PFKFB4 expression by binding to its promoter and mediating transcriptional repression via histone deacetylases
the enzyme is induced in hypoxia and upregulated as a consequence of the transcriptional changes orchestrated by the androgen receptor in prostate cancer cells
-
the enzyme isoform PFKFB4 is about 3fold overexpressed in lung adenocarcinoma compared to normal lung tissue. PFKFB4 mRNA and protein expression are also increased by hypoxia
the protein levels are markedly elevated in high-grade astrocytomas relative to low-grade astrocytomas and corresponding non-neoplastic brain tissue, whereas no significant increase of PFKFB3 mRNA is observed in high-grade astrocytomas
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
pharmacology
-
a pharmacophore map is generated and validated to identify inhibitors of the F6P–FBPase complex
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Algaier, J.; Uyeda, K.
Molecular cloning, sequence analysis, and expression of a human liver cDNA coding for fructose-6-P,2-kinase:fructose-2,6-bisphosphatase
Biochem. Biophys. Res. Commun.
153
328-333
1988
Homo sapiens
Manually annotated by BRENDA team
Sakakibara, R.; Uemura, M.; Hirata, T.; Okamura, N.; Kato, M.
Human placental fructose-6-phosphate,2-kinase/fructose-2,6-bisphosphatase: its isozymic form, expression and characterization
Biosci. Biotechnol. Biochem.
61
1949-1952
1997
Homo sapiens
Manually annotated by BRENDA team
Sakakibara, R.; Kato, M.; Okamura, N.; Nakagawa, T.; Komada, Y.; Tominaga, N.; Shimojo, M.; Fukasawa, M.
Characterization of a human placental fructose-6-phosphate,2-kinase fructose-2,6-bisphosphatase
J. Biochem.
122
122-128
1997
Homo sapiens
Manually annotated by BRENDA team
Lee, Y.H.; Li, Y.; Uyeda, K.; Hasemann, C.A.
Tissue-specific structure/function differentiation of the liver isoform of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
J. Biol. Chem.
278
523-530
2003
Homo sapiens (P16118), Homo sapiens
Manually annotated by BRENDA team
Kessler, R.; Eschrich, K.
Splice isoforms of ubiquitous 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in human brain
Brain Res.
87
190-195
2001
Homo sapiens (Q9BQU3), Homo sapiens
Manually annotated by BRENDA team
Okar, D.A.; Wu, C.; Lange, A.J.
Regulation of the regulatory enzyme, 6-phosphofructo-2-kinase/fructose-2 6-biphosphatase
Adv. Enzyme Regul.
44
123-154
2004
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Rider, M.H.; Bertrand, L.; Vertommen, D.; Michels, P.A.; Rousseau, G.G.; Hue, L.
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase: head-to-head with a bifunctional enzyme that controls glycolysis
Biochem. J.
381
561-579
2004
Arabidopsis thaliana (Q9MB58), Bos taurus (P26285), Bos taurus (P49872), Bos taurus (Q28901), Desulfovibrio desulfuricans, Drosophila melanogaster (Q9VWH7), Homo sapiens (O60825), Homo sapiens (P16118), Homo sapiens (Q16875), Homo sapiens (Q16877), Leishmania major, Mus musculus (P70265), Mus musculus (Q9ESY2), Rattus norvegicus (O35552), Rattus norvegicus (P07953), Rattus norvegicus (P25114), Rattus norvegicus (Q9JJH5), Schizosaccharomyces pombe
Manually annotated by BRENDA team
Minchenko, O.H.; Ochiai, A.; Opentanova, I.L.; Ogura, T.; Minchenko, D.O.; Caro, J.; Komisarenko, S.V.; Esumi, H.
Overexpression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-4 in the human breast and colon malignant tumors
Biochimie
87
1005-1010
2005
Homo sapiens
Manually annotated by BRENDA team
Atsumi, T.; Nishio, T.; Niwa, H.; Takeuchi, J.; Bando, H.; Shimizu, C.; Yoshioka, N.; Bucala, R.; Koike, T.
Expression of inducible 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase/PFKFB3 isoforms in adipocytes and their potential role in glycolytic regulation
Diabetes
54
3349-3357
2005
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Kim, S.G.; Manes, N.P.; El-Maghrabi, M.R.; Lee, Y.H.
Crystal structure of the hypoxia-inducible form of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3): a possible new target for cancer therapy
J. Biol. Chem.
281
2939-2944
2006
Homo sapiens (P16118), Homo sapiens
Manually annotated by BRENDA team
Minchenko, O.H.; Ogura, T.; Opentanova, I.L.; Minchenko, D.O.; Esumi, H.
Splice isoform of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-4: expression and hypoxic regulation
Mol. Cell. Biochem.
280
227-234
2005
Homo sapiens (Q16877)
Manually annotated by BRENDA team
Chesney, J.
6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase and tumor cell glycolysis
Curr. Opin. Clin. Nutr. Metab. Care
9
535-539
2006
Homo sapiens
Manually annotated by BRENDA team
Arden, C.; Hampson, L.J.; Huang, G.C.; Shaw, J.A.; Aldibbiat, A.; Holliman, G.; Manas, D.; Khan, S.; Lange, A.J.; Agius, L.
A role for PFK-2/FBPase-2 as distinct from fructose 2,6-bisphosphate in regulation of insulin secretion in pancreatic beta-cells
Biochem. J.
411
41-51
2007
Homo sapiens, Mus musculus, Mus musculus C57/BL6, Rattus norvegicus, Rattus norvegicus Wistar
Manually annotated by BRENDA team
Kim, S.G.; Cavalier, M.; El-Maghrabi, M.R.; Lee, Y.H.
A direct substrate-substrate interaction found in the kinase domain of the bifunctional enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
J. Mol. Biol.
370
14-26
2007
Homo sapiens
Manually annotated by BRENDA team
Shaikh, M.S.; Mittal, A.; Bharatam, P.V.
Design of fructose-2,6-bisphosphatase inhibitors: A novel virtual screening approach
J. Mol. Graph. Model.
26
900-906
2008
Homo sapiens
Manually annotated by BRENDA team
Kessler, R.; Bleichert, F.; Warnke, J.P.; Eschrich, K.
6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3) is up-regulated in high-grade astrocytomas
J. Neurooncol.
86
257-264
2008
Homo sapiens
Manually annotated by BRENDA team
Myers, R.W.; Baginsky, W.F.; Gattermeir, D.J.; Geissler, W.M.; Harris, G.
Enzymatic preparation of high-specific-activity beta-D-[6,6-3H]fructose-2,6-bisphosphate: application to a sensitive assay for fructose-2,6-bisphosphatase
Anal. Biochem.
406
97-104
2010
Homo sapiens
Manually annotated by BRENDA team
Crochet, R.B.; Cavalier, M.C.; Seo, M.; Kim, J.D.; Yim, Y.S.; Park, S.J.; Lee, Y.H.
Investigating: a case study for small molecule kinases
Anal. Biochem.
418
143-148
2011
Homo sapiens
Manually annotated by BRENDA team
Moon, J.S.; Jin, W.J.; Kwak, J.H.; Kim, H.J.; Yun, M.J.; Kim, J.W.; Park, S.W.; Kim, K.S.
Androgen stimulates glycolysis for de novo lipid synthesis by increasing the activities of hexokinase 2 and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 in prostate cancer cells
Biochem. J.
433
225-233
2011
Homo sapiens
Manually annotated by BRENDA team
Brooke, D.G.; van Dam, E.M.; Watts, C.K.; Khoury, A.; Dziadek, M.A.; Brooks, H.; Graham, L.J.; Flanagan, J.U.; Denny, W.A.
Targeting the Warburg Effect in cancer; relationships for 2-arylpyridazinones as inhibitors of the key glycolytic enzyme 6-phosphofructo-2-kinase/2,6-bisphosphatase 3 (PFKFB3)
Bioorg. Med. Chem.
22
1029-1039
2014
Homo sapiens
Manually annotated by BRENDA team
Ros, S.; Schulze, A.
Balancing glycolytic flux: the role of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatases in cancer metabolism
Cancer Metab.
1
8-8
2013
Homo sapiens
Manually annotated by BRENDA team
Novellasdemunt, L.; Tato, I.; Navarro-Sabate, A.; Ruiz-Meana, M.; Mendez-Lucas, A.; Perales, J.C.; Garcia-Dorado, D.; Ventura, F.; Bartrons, R.; Rosa, J.L.
Akt-dependent activation of the heart 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB2) isoenzyme by amino acids
J. Biol. Chem.
288
10640-10651
2013
Rattus norvegicus, Homo sapiens (O60825), Homo sapiens
Manually annotated by BRENDA team
Chesney, J.; Clark, J.; Klarer, A.C.; Imbert-Fernandez, Y.; Lane, A.N.; Telang, S.
Fructose-2,6-bisphosphate synthesis by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) is required for the glycolytic response to hypoxia and tumor growth
Oncotarget
5
6670-6686
2014
Homo sapiens (Q16877), Homo sapiens
Manually annotated by BRENDA team
Cavalier, M.C.; Kim, S.G.; Neau, D.; Lee, Y.H.
Molecular basis of the fructose-2,6-bisphosphatase reaction of PFKFB3: transition state and the C-terminal function
Proteins
80
1143-1153
2012
Homo sapiens (Q16875), Homo sapiens
Manually annotated by BRENDA team
Lea, M.A.; Guzman, Y.; Desbordes, C.
Inhibition of growth by combined treatment with inhibitors of lactate dehydrogenase and either phenformin or inhibitors of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3
Anticancer Res.
36
1479-1488
2016
Homo sapiens (Q16875)
Manually annotated by BRENDA team
Yalcin, A.; Solakoglu, T.H.; Ozcan, S.C.; Guzel, S.; Peker, S.; Celikler, S.; Balaban, B.D.; Sevinc, E.; Gurpinar, Y.; Chesney, J.A.
6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase-3 is required for transforming growth factor beta1-enhanced invasion of Panc1 cells invitro
Biochem. Biophys. Res. Commun.
484
687-693
2017
Homo sapiens (Q16875)
Manually annotated by BRENDA team
Ros, S.; Floeter, J.; Kaymak, I.; Da Costa, C.; Houddane, A.; Dubuis, S.; Griffiths, B.; Mitter, R.; Walz, S.; Blake, S.; Behrens, A.; Brindle, K.M.; Zamboni, N.; Rider, M.H.; Schulze, A.
6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 is essential for p53-null cancer cells
Oncogene
36
3287-3299
2017
Homo sapiens (Q16877)
Manually annotated by BRENDA team
Du, J.Y.; Wang, L.F.; Wang, Q.; Yu, L.D.
miR-26b inhibits proliferation, migration, invasion and apoptosis induction via the downregulation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 driven glycolysis in osteosarcoma cells
Oncol. Rep.
33
1890-1898
2015
Homo sapiens (Q16875), Homo sapiens
Manually annotated by BRENDA team
Yan, S.; Wei, X.; Xu, S.; Sun, H.; Wang, W.; Liu, L.; Jiang, X.; Zhang, Y.; Che, Y.
6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 spatially mediates autophagy through the AMPK signaling pathway
Oncotarget
8
80909-80922
2017
Homo sapiens (Q16875)
Manually annotated by BRENDA team
Crochet, R.; Kim, J.; Lee, H.; Yim, Y.; Kim, S.; Neau, D.; Lee, Y.
Crystal structure of heart 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB2) and the inhibitory influence of citrate on substrate binding
Proteins
85
117-124
2017
Homo sapiens (O60825), Homo sapiens, Bos taurus (P26285), Bos taurus
Manually annotated by BRENDA team