Information on EC 2.7.1.105 - 6-phosphofructo-2-kinase

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

EC NUMBER
COMMENTARY hide
2.7.1.105
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RECOMMENDED NAME
GeneOntology No.
6-phosphofructo-2-kinase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + beta-D-fructose 6-phosphate = ADP + beta-D-fructose 2,6-bisphosphate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
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-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
fructose 2,6-bisphosphate biosynthesis
-
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Fructose and mannose metabolism
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SYSTEMATIC NAME
IUBMB Comments
ATP:beta-D-fructose-6-phosphate 2-phosphotransferase
Not identical with EC 2.7.1.11 6-phosphofructokinase. The enzyme co-purifies with EC 3.1.3.46 fructose-2,6-bisphosphate 2-phosphatase.
CAS REGISTRY NUMBER
COMMENTARY hide
78689-77-7
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
cv. Columbia
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-
Manually annotated by BRENDA team
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SwissProt
Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
Jerusalem artichoke
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-
Manually annotated by BRENDA team
gene PFKFB3, isozyme iPFK2 is inducible
SwissProt
Manually annotated by BRENDA team
crayfish
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-
Manually annotated by BRENDA team
frog
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-
Manually annotated by BRENDA team
gene/isozyme PFKFB2
SwissProt
Manually annotated by BRENDA team
gene Pfkfb1
SwissProt
Manually annotated by BRENDA team
castor bean
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-
Manually annotated by BRENDA team
potato plant, enzyme of Solanum tuberosum is 83% identical with enzyme of Zea mays and 72% identical with enzyme of Pinus taeda
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
Pfkfb (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase) enzymes are bi-functional enzymes encoded by four different genes (pfkfb1, pfkfb2, pfkfb3, pfkfb4) in vertebrates, phylogenetic analysis of Pfkfb enzymes in vertebrates, overview; Pfkfb (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase) enzymes are bi-functional enzymes encoded by four different genes (pfkfb1, pfkfb2, pfkfb3, pfkfb4) in vertebrates, phylogenetic analysis of Pfkfb enzymes in vertebrates, overview; Pfkfb (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase) enzymes are bi-functional enzymes encoded by four different genes (pfkfb1, pfkfb2, pfkfb3, pfkfb4) in vertebrates, phylogenetic analysis of Pfkfb enzymes in vertebrates, overview
malfunction
metabolism
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ADP + beta-D-fructose 2,6-bisphosphate
ATP + beta-D-fructose 6-phosphate
show the reaction diagram
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reverse reaction, at 50% the rate of forward reaction
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r
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
show the reaction diagram
ATP + D-fructose 6-phosphate
ADP + D-fructose 2,6-bisphosphate
show the reaction diagram
-
-
-
-
?
ATP + D-psicose 6-phosphate
?
show the reaction diagram
-
-
-
-
?
ATP + D-tagatose 6-phosphate
?
show the reaction diagram
-
-
-
-
?
ATP + L-sorbose 6-phosphate
?
show the reaction diagram
-
-
-
-
?
CTP + D-fructose 6-phosphate
CDP + beta-D-fructose 2,6-bisphosphate
show the reaction diagram
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-
-
-
?
GTP + beta-D-fructose 6-phosphate
GDP + beta-D-fructose 2,6-bisphosphate
show the reaction diagram
ITP + beta-D-fructose 6-phosphate
IDP + beta-D-fructose 2,6-bisphosphate
show the reaction diagram
-
-
-
-
?
MgATP2- + beta-D-fructose 6-phosphate
?
show the reaction diagram
UTP + D-fructose 6-phosphate
UDP + beta-D-fructose 2,6-bisphosphate
show the reaction diagram
-
-
-
-
?
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + beta-D-fructose 6-phosphate
ADP + beta-D-fructose 2,6-bisphosphate
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
GMP
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activation
IMP
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activation
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
AsO43-
phosphate
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2E)-1-(pyridin-4-yl)-3-(quinolin-2-yl)prop-2-en-1-one
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(2E)-3-(pyridin-3-yl)-1-(pyridin-4-yl)prop-2-en-1-one
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1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one
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the inhibitor causes a rapid induction of apoptosis in transformed cells, has adequate pharmacokinetic properties, suppresses the glucose uptake and growth of Lewis lung carcinomas in syngeneic mice and yields anti-tumor effects in three human xenograft models of cancer in athymic mice that are comparable to FDA-approved chemotherapeutic agents
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2,5-anhydro-D-mannitol 6-phosphate
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2-((5-bromo-6-oxo-1-phenyl-1,6-dihydropyridazin-4-yl)amino)acetamide
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2-(5-bromo-6-oxo-1-phenyl-1,6-dihydropyridazin-4-yl)-1,2,3,4-tetrahydroisoquinoline-5-carbonitrile
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-
2-hydroxy-4-[(naphthalen-1-ylsulfonyl)amino]benzoic acid
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3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one
3-phosphoglycerate
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3H-benzo[e]indol-2-yl(pyridin-4-yl)methanone
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4-(4-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-5-bromo-6-oxopyridazin-1(6H)-yl)benzonitrile
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4-bromo-2-phenyl-5-(((tetrahydrofuran-2-yl)methyl)amino)pyridazin-3(2H)-one
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4-bromo-2-phenyl-5-(2-oxa-6-azaspiro[3.3]heptan-6-yl)pyridazin-3(2H)-one
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4-bromo-5-morpholino-2-phenylpyridazin-3(2H)-one
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5,6,7,8-tetrahydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one
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5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-2-benzyl-4-bromopyridazin-3(2H)-one
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5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-2-benzylpyridazin-3(2H)-one
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5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(3-phenylpropyl)pyridazin-3(2H)-one
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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
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5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(4-(trifluoromethoxy)phenyl)-pyridazin-3(2H)-one
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5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(4-chlorophenyl)pyridazin-3(2H)-one
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5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(4-iodobenzyl)pyridazin-3(2H)-one
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5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-(pyrimidin-5-yl)pyridazin-3(2H)-one
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5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-phenethylpyridazin-3(2H)-one
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5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-bromo-2-phenylpyridazin-3(2H)-one
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5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-chloro-2-phenylpyridazin-3(2H)-one
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5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-ethoxy-2-phenylpyridazin-3(2H)-one
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5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-iodo-2-phenylpyridazin-3(2H)-one
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5-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-4-isopropyl-2-phenylpyridazin-3(2H)-one
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5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside
AICAR, associated with phosphorylation of PFK-2 on Ser-32, phosphorylation increased of both wild-type and overexpressed PFK-2 protein in hepatocytes
7,8-dihydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one
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beta-D-fructose 2,6-bisphosphate
beta-D-fructose 6-phosphate
modeling of beta-D-fructose 6-phosphate as inhibitor
citrate
dibutyryl cAMP
slightly inhibits the complex formation between the enzyme and glucokinase
dihydroxyacetone phosphate
diphosphate
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
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glucagon
glycerate 2-phosphate
Glycerol 2-phosphate
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glycerol 3-phosphate
20% inhibition at 2mM
glycolate 2-phosphate
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guanidine
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inactivation, unfolding
m-periodate
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strong, DTT protects or reverses
Mg2+
-
MgATP
MgATP
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inhibited by, structure determination reveals substrate inhibition due to sequential binding of two MgATP molecules per subunit, the first at the usual site occupied by the nucleotide in homologous enzymes and the second at the allosteric site, making a number of direct and Mg-mediated interactions with the first, two configurations observed for the second MgATP, one of which involves interactions with Tyr-23 from the adjacent subunit in the dimer and the other making an unusual non-Watson-Crick base pairing with the adenine in the substrate ATP
MgATP2-
MgNTP
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strain DF903, substrate inhibition, most effective: MgATP2, at low fructose concentration
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N-(1-pyrenil)maleimide
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complete loss of catalytic activity, but modified enzyme is able to bind beta-D-fructose 6-phosphate, the presence of MgATP2- completely protects the enzyme activity, the modified enzyme elutes as a monomer
N-bromoacetyletanolamine phosphate
an irreversible inhibitor of PFK-2 in several cancer cell lines
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N-Bromoacetylethanolamine
o-phthalaldehyde
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kinetics, DTT or substrates do not protect
phosphate
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inhibits wild-type and mutant enzym E190Q. E190 contributs to the mechanism of phosphate inhibition in Pfk-2. E190Q mutant presents alterations in the inhibition by MgATP2- and phosphate
phosphoenolpyruvate
protein kinase A
inactivation via a 7fold increase in Km for fructose 6-phosphate without alteration of Vmax
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pyrene maleimide
-
incorporation of 2 mol per mol of enzyme subunit, modifiying Cys-238 and Cys-295, leads to rapid inactivation, MgATP2- protects Cys295, modification of Cys238 does not abolish activity
sn-glycerol 3-phosphate
additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
glucose
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inhibition by N-bromoacetylethanolamine
Insulin
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iodoacetamide
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00087 - 1.62
ATP
0.02 - 0.21
beta-D-fructose 2,6-bisphosphate
0.0038 - 39
beta-D-fructose 6-phosphate
0.9 - 2
CTP
0.0094 - 0.1
D-fructose 6-phosphate
7.4
D-psicose 6-phosphate
-
pH 7.5, 30°C
15
D-tagatose 6-phosphate
-
pH 7.5, 30°C
0.35 - 1.5
GTP
0.3
ITP
-
pH 8.2, 30°C, strain DF903
0.175
L-Sorbose 6-phosphate
-
pH 7.5, 30°C
0.0072 - 2
MgATP2-
0.78 - 2.3
UTP
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.14 - 0.19
ATP
0.14 - 9320
beta-D-fructose 6-phosphate
0.14 - 53
D-fructose 6-phosphate
0.14 - 9320
MgATP2-
additional information
additional information
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.095
2,5-anhydro-D-mannitol 6-phosphate
-
pH 7.5, 30°C
0.025
3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one
-
inhibition of recombinant PFKFB3 protein, no inhibition of purified PFK-1 activity
0.16
ADP
-
pH 6.6, 25°C
0.008 - 0.01
ATP
8.5 - 13.4
beta-D-fructose 6-phosphate
0.025 - 6
citrate
0.25 - 1.9
dihydroxyacetone phosphate
0.026 - 0.16
diphosphate
0.016 - 0.45
glycerate 2-phosphate
0.084
Glycerate 3-phosphate
pH 7.8, 25°C
0.02 - 0.18
glycolate 2-phosphate
2 - 15
N-Bromoacetylethanolamine
0.028
o-phthalaldehyde
-
pH 7.4, room temperature
0.014 - 2.3
phosphoenolpyruvate
0.018 - 8.07
sn-glycerol 3-phosphate
additional information
additional information
-