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Information on EC 2.7.1.40 - pyruvate kinase and Organism(s) Oryctolagus cuniculus and UniProt Accession P11974
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2.7.1.40 pyruvate kinaseIUBMB Comments
UTP, GTP, CTP, ITP and dATP can also act as donors. Also phosphorylates hydroxylamine and fluoride in the presence of CO2.
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Word Map
- 2.7.1.40
- hexokinase
-
phosphofructokinase
- erythrocyte
- fructose
- glucose-6-phosphate
- hepatocytes
- glycogen
- anemia
-
carboxykinase
-
gluconeogenesis
- aldolase
- pep
-
hemolytic
- malate
- citrate
- creatine
- glucokinase
- adenylate
- carboxylase
-
warburg
-
gluconeogenic
- enolase
- phosphoglycerate
- pentose
- 6-phosphate
-
malic
- glucagon
- glyceraldehyde-3-phosphate
- reticulocyte
-
lipogenesis
- 6-phosphogluconate
- fructose-1,6-bisphosphate
-
lipogenic
- 2,6-bisphosphate
- g6pase
-
1,6-bisphosphatase
-
liver-type
-
splenectomy
- hk2
- dikinase
-
glutaminolysis
-
calprotectin
- triose
- shikonin
- 2,3-diphosphoglycerate
- fructose-6-phosphate
-
glycogenolysis
- drug development
- medicine
- biofuel production
-
reticulocytosis
-
transfusion-dependent
-
spherocytosis
- nutrition
- diagnostics
The taxonomic range for the selected organisms is: Oryctolagus cuniculus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
pyruvate kinase, m2-pk, pyruvate kinase m2, l-pk, pyk, tum2-pk, pyruvate kinase type m2, liver pyruvate kinase, pyruvate kinase m2 isoform, m2-pyruvate kinase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CTHBP
-
-
-
-
cytosolic thyroid hormone binding protein
-
-
-
-
fluorokinase
-
-
-
-
kinase, fluoro- (phosphorylating)
-
-
-
-
kinase, pyruvate (phosphorylating)
-
-
-
-
L-PK
-
-
-
-
M1-PK
phosphoenol transphosphorylase
-
-
-
-
phosphoenolpyruvate kinase
-
-
-
-
pyruvate kinase muscle isozyme
-
-
-
-
pyruvate phosphotransferase
pyruvic kinase
-
-
-
-
R-type/L-type pyruvate kinase
-
-
-
-
red cell/liver pyruvate kinase
-
-
-
-
THBP1
-
-
-
-
VEG17
-
-
-
-
vegetative protein 17
-
-
-
-
pyruvate phosphotransferase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
-
-, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
ATP:pyruvate 2-O-phosphotransferase
UTP, GTP, CTP, ITP and dATP can also act as donors. Also phosphorylates hydroxylamine and fluoride in the presence of CO2.
CAS REGISTRY NUMBER
COMMENTARY
9001-59-6
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
dADP + phosphoenolpyruvate
dATP + pyruvate
9.9% activity compared to ADP
-
-
?
dCDP + phosphoenolpyruvate
dCTP + pyruvate
0.082% activity compared to ADP
-
-
?
dGDP + phosphoenolpyruvate
dGTP + pyruvate
1.82% activity compared to ADP
-
-
?
dTDP + phosphoenolpyruvate
dTTP + pyruvate
0.035% activity compared to ADP
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
-
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
100% activity with ADP
-
-
?
additional information
?
-
-
the recombinant enzyme shows the following range in its substrate specificity: ADP>dADP>dGDP>dCDP>TDP
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
K+
Mg2+
Mn2+
Na+
-
in aqueous media, muscle pyruvate kinase is highly selective for K+ over Na+. Dimethylsulfoxide favors the partition of K+ and Na+ into the monovalent and divalent cation binding sites of the enzyme. The kinetics of the enzyme at subsaturating concentrations of activators show that K+ and Mg2+ exhibit high selectivity for their respective cation binding sites, whereas when Na+ substitutes K+, Na+ and Mg2+ bind with high affinity to their incorrect sites. The ratio of the affnities of Mg2+ and K+ for the monovalent cation binding site is close to 200. For Na+ and Mg2+ this ratio is approximately 20. The data suggest that K+ induces conformational hanges that prevent the binding of Mg2+ to the monovalent cation binding site
additional information
K+
-
in aqueous media, muscle pyruvate kinase is highly selective for K+ over Na+. Dimethylsulfoxide favors the partition of K+ and Na+ into the monovalent and divalent cation binding sites of the enzyme. The kinetics of the enzyme at subsaturating concentrations of activators show that K+ and Mg2+ exhibit high selectivity for their respective cation binding sites, whereas when Na+ substitutes K+, Na+ and Mg2+ bind with high affinity to their incorrect sites. The ratio of the affnities of Mg2+ and K+ for the monovalent cation binding site is close to 200. For Na+ and Mg2+ this ratio is approximately 20. The data suggest that K+ induces conformational changes that prevent the binding of Mg2+ to the monovalent cation binding site
K+
-
K+ is directly involved in the acquisition of the active conformation and movement of the B domain of the enzyme
Mg2+
-
kinetics of the enzyme at subsaturating concentrations of activators show that K+ and Mg2+ exhibit high selectivity for their respective cation binding sites, whereas when Na+ substitutes K+, Na+ and Mg2+ bind with high affinity to their incorrect sites. The ratio of the affinities of Mg2+ and K+ for the monovalent cation binding site is close to 200. For Na+ and Mg2+ this ratio is approximately 20
Mg2+
-
addition of Mg2+ protects the enzyme completely from the ferrous ion-mediated inactivation
additional information
-
enzyme spectra in the absence and presence of activating cations, overview
additional information
-
interaction of three Trp residues, Tr157, Trp481, and Trp514, with activating cations, overview. The majority of changes in tryptophan fluorescence signal from PK induced by the binding of activating cations come from Trp157. Interactions with Mg2+ and K+ lead to more exposed tryptophan residues of PK while interactions with phosphoenolpyruvate and ADP decrease solvent accessibility of the tryptophan residues
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ascorbate
-
treatment of rabbit muscle pyruvate kinase with 10 mM ascorbate causes an inactivation with the cleavage of peptide bond. The inactivation or fragmentation of the enzyme is prevented by addition of Mg2+, catalase, and mannitol, but ADP and PEP the substrates do not show any effect
FeSO4
-
treatment of rabbit muscle pyruvate kinase with 0.02 mM FeSO4 causes an inactivation with the cleavage of peptide bond. The inactivation or fragmentation of the enzyme is prevented by addition of Mg2+, catalase, and mannitol, but ADP and PEP the substrates do not show any effect
Procion blue MX-R
-
triazine dye, kinetics, ADP or ADP plus Mg2+ protect, not Mg2+ alone
L-phenylalanine
-
acts as an allosteric inhibitor of muscle isozyme and induces the enzyme to exist in multiple conformations by locking it in an expanded or asymmetric conformation, which is contrary effect to that of phosphoenolpyruvate binding
L-phenylalanine
-
the carboxyl group of phosphoenolpyruvate is responsible for energetic coupling with Phe binding in the allosteric sites
phenylalanine
-
allosteric inhibitor, regions of pyruvate kinase important for allosteric regulation by phenylalanine, H/D exchange mass spectrometry, overview
additional information
not inhibited by propionic acid, N-methyl-L-alanine, N-formyl-L-alanine, N-acetyl-L-alanine, 3 phenylpropionic acid, N-methyl-L-phenylalanine, N-formyl-L-phenylalanine, N-acetyl-L-phenylalanine, and N,N-dimethylphenylalanine
-
additional information
-
alanine is a nonallosteric analogue of phenylalanine, it binds competitively with phenylalanine but elicits a negligible allosteric inhibition, i.e., a negligible reduction in the affinity of the muscle enzyme for the substrate, phosphoenolpyruvate
-
additional information
-
interactions with Mg2+ and K+ lead to more exposed tryptophan residues of PK while interactions with phosphoenolpyruvate and ADP decrease solvent accessibility of the tryptophan residues
-
additional information
-
replacing the carboxyl group of the substrate with a methyl alcohol or removing the phosphate altogether greatly reduces substrate affinity. Removal of the carboxyl group is the only modification tested that removes the ability to allosterically reduce the level of Phe binding. Requirement for monovalent and divalent cations for allosteric inhibition
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
23
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
additional information
physiological function
-
required role of the active site in allosteric regulation involving substrate binding, requirement for monovalent and divalent cations, overview
additional information
-
catalysis by muscle pyruvate kinase involves domain movements and conformational changes induced by activating cations and its substrates. Fluorescence acrylamide quenching analyses reveal that interactions with Mg2+ and K+ lead to a more exposed active site of the enzyme while interactions with phosphoenolpyruvate and ADP decrease solvent accessibility of the active site, overview
additional information
-
movement of the B domain is essential for the catalytic reaction. Rotation of the B domain in the opening of the cleft between domains B and A induced by the binding of activating cations allows substrates to bind, whereas substrate binding shifts the rotation of the B domain in the closure of the cleft. The enzyme exhibits a more dynamic structure after binding of activating metal ions and substrates, whereas binding of Phe decreases the dynamics
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). KPYM_RABIT
531
0
58048
Swiss-Prot
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homotetramer
homotetramer
-
secondary and tertiary structure of muscle isozyme homotetramer and the four monomers with three tryptophans Trp157, Trp481, and Trp514, and bound Mg2+ and K+ per monomer, each monomer consists of the N-terminal domain, domain A, domain B, and domain C, overview
homotetramer
-
structure of muscle isozyme homotetramer and of the four monomers with Y-interface and Z-interface, each monomer consists of the N-terminal domain, domain A, domain B, and domain C, overview
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging drop vapour diffusion method using 60 mM succinate (pH 5.5), 5.8 mM sodium pyruvate, 2.4 mM MnCl2, 450 mM KCl, and a range of 18 to 20% PEG 8000
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
S240P
the mutant exhibits steady-state kinetic behavior that indicates that it is more responsive to regulation by effectors
W157A
-
site-directed mutagenesis, Trp157 is located in domain B and close to the active site
W481A/W514A
-
site-directed mutagenesis, Trp481 and Trp514 are located in domain C and close to the Y-interface
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
partially purified enzyme preparations from various organisms: overview
-
recombinant wild-type and mutant enzymes in Escherichia coli strain BL21
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of wild-type and mutant enzymes in Escherichia coli strain BL21
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Schmidt-Base, K.; Buchbinder, J.L.; Reed, G.H.; Rayment, I.
Crystallization and preliminary analysis of enzyme-substrate complexes of pyruvate kinase from rabbit muscle
Proteins Struct. Funct. Genet.
11
153-157
1991
Oryctolagus cuniculus
Guy, E.C.; Giles, I.G.
Studies on the inhibition of type-M pyruvate kinase by the triazine dye ProcionBlue MX-R
Biochem. Soc. Trans.
14
152
1986
Oryctolagus cuniculus
-
Kayne, F.J.
Pyruvate kinase
The Enzymes,3rd Ed. (Boyer,P. D. ,ed. )
8
353-382
1973
Azotobacter vinelandii, Komagataeibacter xylinus, Antarctic fish, Bacillus subtilis, [Brevibacterium] flavum, Saccharomyces cerevisiae, Coprinopsis lagopus, Oryctolagus cuniculus, Schistocerca gregaria, Escherichia coli, Euglena gracilis, Cobitidae, Amylomyces rouxii, Mus musculus, Oncorhynchus mykiss, Ostreidae, Paralithodes camtschaticus, Lithobates pipiens, Rattus norvegicus, Saccharomyces pastorianus, Sus scrofa, Halothiobacillus neapolitanus, Trypanosoma brucei
-
Ramirez-Silva, L.; Oria-Hernandez, J.
Selectivity of pyruvate kinase for Na+ and K+ in water/dimethylsulfoxide mixtures
Eur. J. Biochem.
270
2377-2385
2003
Oryctolagus cuniculus
Williams, R.; Holyoak, T.; McDonald, G.; Gui, C.; Fenton, A.W.
Differentiating a ligands chemical requirements for allosteric interactions from those for protein binding. Phenylalanine inhibition of pyruvate kinase
Biochemistry
45
5421-5429
2006
Oryctolagus cuniculus (P11974)
Lee, J.C.
Modulation of allostery of pyruvate kinase by shifting of an ensemble of microstates
Acta Biochim. Biophys. Sin.
40
663-669
2008
Oryctolagus cuniculus (P11974)
Herman, P.; Lee, J.C.
Functional energetic landscape in the allosteric regulation of muscle pyruvate kinase. 1. Calorimetric study
Biochemistry
48
9448-9455
2009
Oryctolagus cuniculus
Herman, P.; Lee, J.C.
Functional energetic landscape in the allosteric regulation of muscle pyruvate kinase. 2. Fluorescence study
Biochemistry
48
9456-9465
2009
Oryctolagus cuniculus
Herman, P.; Lee, J.C.
Functional energetic landscape in the allosteric regulation of muscle pyruvate kinase. 3. Mechanism
Biochemistry
48
9466-9470
2009
Oryctolagus cuniculus
Murakami, K.; Tsubouchi, R.; Fukayama, M.; Qiao, S.; Yoshino, M.
Iron-dependent oxidative inactivation with affinity cleavage of pyruvate kinase
Biol. Trace Elem. Res.
130
31-38
2009
Oryctolagus cuniculus
Gao, S.; Bao, J.; Gu, X.; Xin, X.; Chen, C.; Ryu, D.
Substrate promiscuity of pyruvate kinase on various deoxynucleoside diphosphates for synthesis of deoxynucleoside triphosphates
Enzyme Microb. Technol.
43
455-459
2008
Bacillus sp. (in: Bacteria), Zymomonas mobilis, Oryctolagus cuniculus (P11974)
-
Urness, J.M.; Clapp, K.M.; Timmons, J.C.; Bai, X.; Chandrasoma, N.; Buszek, K.R.; Fenton, A.W.
Distinguishing the chemical moiety of phosphoenolpyruvate that contributes to allostery in muscle pyruvate kinase
Biochemistry
52
1-3
2013
Oryctolagus cuniculus
Prasannan, C.B.; Villar, M.T.; Artigues, A.; Fenton, A.W.
Identification of regions of rabbit muscle pyruvate kinase important for allosteric regulation by phenylalanine, detected by H/D exchange mass spectrometry
Biochemistry
52
1998-2006
2013
Oryctolagus cuniculus
Li, F.; Yu, T.; Zhao, Y.; Yu, S.
Probing the catalytic allosteric mechanism of rabbit muscle pyruvate kinase by tryptophan fluorescence quenching
Eur. Biophys. J.
41
607-614
2012
Oryctolagus cuniculus
Ou, Y.; Tao, W.; Zhang, Y.; Wu, G.; Yu, S.
The conformational change of rabbit muscle pyruvate kinase induced by activating cations and its substrates
Int. J. Biol. Macromol.
47
228-232
2010
Oryctolagus cuniculus
Boehme, C.; Bieber, F.; Linnemann, J.; Breitling, R.; Lorkowski, S.; Reissmann, S.
Chemical and enzymatic characterization of recombinant rabbit muscle pyruvate kinase
Biol. Chem.
394
695-701
2013
Oryctolagus cuniculus
Strumilo, S.; Tylicki, A.
Dissimilar properties of pyruvate kinase from rabbit and hare muscle
J. Evol. Biochem. Physiol.
51
117-121
2015
Oryctolagus cuniculus, Lepus europaeus
-
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