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Information on EC 2.7.1.40 - pyruvate kinase and Organism(s) Leishmania mexicana and UniProt Accession Q27686
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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: Leishmania mexicana
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
-
-
-
-
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
-
-
-
-
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
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
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3-(2,5-dimethylphenoxy)-1,2-benzothiazole 1,1-dioxide
-
a saccharin derivative, potent inhibitor, but a labile compound
3-[(2,5-dimethylphenyl)sulfanyl]-1,2-benzothiazole 1,1-dioxide
-
a stable sulfur derivative of 3-(2,5-dimethylphenoxy)-1,2-benzothiazole 1,1-dioxide
4-[(1,1-dioxo-1,2-benzothiazol-3-yl)sulfanyl]benzoic acid
-
irreversible inhibitor, a saccharin derivative, reacts with an active-site lysine residue (Lys335), forming a covalent bond and sterically hindering the binding of ADP/ATP, covalent inhibitor mechanism, overview. Inhibition of LmPYK by the compound is time-dependent
additional information
-
the nitrogen analogue N-(2,5-dimethylphenyl)-1,2-benzothiazol-3-amine 1,1-dioxide of 3-(2,5-dimethylphenoxy)-1,2-benzothiazole 1,1-dioxide is not inhibitory
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
S0.5 value of phosphoenolpyruvate is 1.06 mM for wild-type, 1.3 mM for mutant E451W
-
additional information
additional information
-
S0.5 value of phosphoenolpyruvate is 1.06 mM for wild-type, 1.3 mM for mutant E451W
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.01
3-(2,5-dimethylphenoxy)-1,2-benzothiazole 1,1-dioxide
Leishmania mexicana
-
pH 7.2, 25°C
0.005
3-[(2,5-dimethylphenyl)sulfanyl]-1,2-benzothiazole 1,1-dioxide
Leishmania mexicana
-
pH 7.2, 25°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
the enzyme uses a rock and lock model allosteric mechanism, intersubunit interactions on the A-A and C-C interfaces strongly influence the allosteric effect whereas mutations affecting the intrasubunit A-C interface are less sensitive, overview. Conformational changes coupled with effector binding correlate with loss of flexibility and increase in thermal stability providing a general mechanism for allosteric control
physiological function
-
PYK plays a central role in a number of proliferative and infectious diseases
additional information
additional information
the transition between inactive T-state and active R-state is accompanied by a simple symmetrical 6o rigid body rocking motion of the A- and C-domain cores in each of the four subunits. Eight essential salt bridge locks form across the C-C interface providing tetramer rigidity with a coupled 7fold increase in reaction rate
additional information
-
the transition between inactive T-state and active R-state is accompanied by a simple symmetrical 6o rigid body rocking motion of the A- and C-domain cores in each of the four subunits. Eight essential salt bridge locks form across the C-C interface providing tetramer rigidity with a coupled 7fold increase in reaction rate
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). KPYK_LEIME
499
0
54405
Swiss-Prot
other Location (Reliability: 3)
PDB
SCOP
CATH
UNIPROT
ORGANISM
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homotetramer
enzyme structure in complex with ATP, oxalate, and fructose-2,6-bishosphate, overview
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystals grown with ammonium sulfate as precipitant adopt an active-like conformation, with sulfate ions at the active and effector sites. Crystal soaking in sulfate-free buffers induces major conformational changes in the tetramer. The unwinding of the Aalpha6' helix and the inward hinge movement of the B domain are coupled with a significant widening of the tetramer caused by lateral movement of the C-domains
purified recombinant wild-type and mutant enzymes free and in complex with ligands ATP, oxalate, and fructose 2,6-bisphosphate, hanging drop vapour diffusion method, 0.0015 ml of 15 mg/ml protein in 20 mM TEA, pH 7.2, are mixed with 0.0015 ml of well solution composed of 10-16% PEG 8000, 20 mM TEA, pH 7.2, 50 mM MgCl2, 100 mM KCl, and 10-15% glycerol, 4°C or 17°C, 1week, X-ray diffraction structure determination and analysis
enzyme complexed with inhibitor 4-[(1,1-dioxo-1,2-benzothiazol-3-yl)sulfanyl]benzoic acid, mxing of 0.0015 ml of 10 mg/ml protein in 20 mM TEA, pH 7.2, 1 mM 1,3,6,8-pyrenetetrasulfonic acid, and 9 mM inhibitor, with 0.0015 ml of well solution containing 12-16% PEG 8000, 20 mM TEA buffer, pH 7.2, 50 mM magnesium chloride, 100 mM potassium chloride, and 10% glycerol, 1-2 days, and equilibration for 14 h over a well solution composed of 14-18% PEG 8,000, 20 mM TEA buffer, pH 7.2, 50 mM magnesium chloride, 100 mM potassium chloride, and 25% glycerol, X-ray diffraction structure determination and analysis at 2.65 A resolution
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D315N
3.7% of wild-type activity. S0.5 value for fructose 2,6-bisphosphate 0.001 mM
D315S
1.4% of wild-type activity. S0.5 value for fructose 2,6-bisphosphate 0.00161 mM
E451W
72% of wild-type activity. S0.5 value for fructose 2,6-bisphosphate 0.000177 mM
S314N
69% of wild-type activity. S0.5 value for fructose 2,6-bisphosphate 0.000403 mM
S314Q
48% of wild-type activity. S0.5 value for fructose 2,6-bisphosphate 0.000122 mM
K335R
-
site-directed mutagenesis, structure compared to the wild-type, overview
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
binding of frucctose 2,6-bisphophate plays the most important role in stabilizing the LmPYK tetramer in solution
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant wild-type and mutant enzymes from Escherichia coli strain Bl21(DE3)
recombinant wild-type and mutant enzymes from Escherichia coli strain Rosetta 2 (DE3)pLysS
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of wild-type and mutant enzymes in Escherichia coli strain BL21(DE3), cloning in Escherichia coli strain XL-1 Blue
expression of wild-type and mutant enzymes in Escherichia coli strain Rosetta 2 (DE3)pLysS
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Tulloch, L.B.; Morgan, H.P.; Hannaert, V.; Michels, P.A.; Fothergill-Gilmore, L.A.; Walkinshaw, M.D.
Sulphate removal induces a major conformational change in Leishmania mexicana pyruvate kinase in the crystalline state
J. Mol. Biol.
383
615-626
2008
Leishmania mexicana (Q27686), Leishmania mexicana
Morgan, H.P.; Walsh, M.J.; Blackburn, E.A.; Wear, M.A.; Boxer, M.B.; Shen, M.; Veith, H.; McNae, I.W.; Nowicki, M.W.; Michels, P.A.; Auld, D.S.; Fothergill-Gilmore, L.A.; Walkinshaw, M.D.
A new family of covalent inhibitors block nucleotide binding to the active site of pyruvate kinase
Biochem. J.
448
67-72
2012
Leishmania mexicana
Morgan, H.P.; McNae, I.W.; Nowicki, M.W.; Hannaert, V.; Michels, P.A.; Fothergill-Gilmore, L.A.; Walkinshaw, M.D.
Allosteric mechanism of pyruvate kinase from Leishmania mexicana uses a rock and lock model
J. Biol. Chem.
285
12892-12898
2010
Leishmania mexicana (Q27686), Leishmania mexicana
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