Information on EC 5.4.2.4 - Bisphosphoglycerate mutase

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The expected taxonomic range for this enzyme is: Opisthokonta

EC NUMBER
COMMENTARY
5.4.2.4
-
RECOMMENDED NAME
GeneOntology No.
Bisphosphoglycerate mutase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
3-phospho-D-glyceroyl phosphate = 2,3-bisphospho-D-glycerate
show the reaction diagram
-
-
-
-
3-phospho-D-glyceroyl phosphate = 2,3-bisphospho-D-glycerate
show the reaction diagram
mechanism
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
group transfer
-
-
intramolecular, phosphate group
-
isomerization
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
Rapoport-Luebering glycolytic shunt
-
Glycolysis / Gluconeogenesis
-
Metabolic pathways
-
SYSTEMATIC NAME
IUBMB Comments
3-Phospho-D-glycerate 1,2-phosphomutase
In the direction shown, this enzyme is phosphorylated by 3-phosphoglyceroyl phosphate, to give phosphoenzyme and 3-phosphoglycerate. The latter is rephosphorylated by the enzyme to yield 2,3-bisphosphoglycerate, but this reaction is slowed by dissociation of 3-phosphoglycerate from the enzyme, which is therefore more active in the presence of added 3-phosphoglycerate. This enzyme also catalyses, slowly, the reactions of EC 3.1.3.13 (bisphosphoglycerate phosphatase), EC 5.4.2.11 [phosphoglycerate mutase (2,3-diphosphoglycerate-dependent)] and EC 5.4.2.12 [phosphoglycerate mutase (2,3-diphosphoglycerate-independent)].
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
2,3 bisphosphoglycerate mutase
-
-
2,3-Bisphosphoglycerate mutase
-
-
-
-
2,3-bisphosphoglycerate mutase, erythrocyte
-
-
-
-
2,3-bisphosphoglycerate synthase
-
-
-
-
2,3-Diphosphoglycerate mutase
-
-
-
-
2,3-Diphosphoglycerate synthase
-
-
-
-
2,3-Diphosphoglyceromutase
-
-
-
-
Biphosphoglycerate synthase
-
-
-
-
bisphosphoglycerate mutase
-
-
bisphosphoglycerate mutase
P07738
-
Bisphosphoglyceromutase
-
-
-
-
BPG synthase
-
-
BPG-dependent PGAM
-
-
-
-
BPGAM
P07738
a trifunctional enzyme that possesses mutase, synthase and phosphatase activities
BPGM
-
-
-
-
BPGM
-
-
Diphosphoglycerate mutase
-
-
-
-
Diphosphoglyceric mutase
-
-
-
-
Diphosphoglyceromutase
-
-
-
-
DPGM
-
-
-
-
EC 2.7.5.4
-
-
has mRNA guanylyltransferase and RNA 5'-triphosphatase activity
-
Glycerate phosphomutase
-
-
-
-
Phosphomutase, glycerate (phosphoglycerate cofactor)
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
37211-69-1
-
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
metabolism
-
NO may suppress 2,3-bisphospho-D-glycerate production by (1) inhibiting glyceraldehyde-3-phosphate dehydrogenase, the most critical glycolytic enzyme for the bioavailability of 1,3-bisphosphoglycerate, and to a lesser extent by (2) associated pH changes in the deoxy-hemoglobin-catalyzed depletion of nitrite, a metabolic reservoir of NO
physiological function
-
the enzyme is responsible for biosynthesis of 2,3-bisphospho-D-glycerate, which is an enhancer of oxygen off-loading from hemoglobin. It is very sensitive to changes in glycolytic rates because its synthesis by BPG synthase is dependent on the availability of the glycolytic intermediate 1,3-bisphosphoglycerate, metabolic enzyme regulation, overview
physiological function
-
bisphosphoglycerate mutase is a multi-activity enzyme. Its main function is to synthesize the 2,3-bisphosphoglycerate, the allosteric effector of hemoglobin, the enzyme regulates 2,3-bisphosphoglycerate levels, quantum mechanics/molecular mechanics simulations based on the metadynamics and umbrella sampling simulations, detailed overview
metabolism
-
the main activity of the enzyme is synthase (EC 5.4.2.4), converting 1,3-bisphosphoglycerate to 2,3-bisphosphoglycerate. The second activity is mutase (phosphoglycerate mutase, EC 5.4.2.1), catalyzing the interconversion between 2-phosphoglycerate and 3-phosphoglycerate. The third activity is phosphatase (S-succinylglutathione hydrolase, EC 3.1.3.13), hydrolyzing 2,3-bisphosphoglycerate to 3-phosphoglycerate or 2-phosphoglycerate and phosphate
additional information
-
proposed mechanisms for the phosphatase and the synthase reactions involving residues His11 and Glu89
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1,3-Diphosphoglycerate
2,3-Diphosphoglycerate
show the reaction diagram
-
-
-
-
1,3-Diphosphoglycerate
2,3-Diphosphoglycerate
show the reaction diagram
-
-
-
-
-
1,3-Diphosphoglycerate
2,3-Diphosphoglycerate
show the reaction diagram
-
-
-
-
1,3-Diphosphoglycerate
2,3-Diphosphoglycerate
show the reaction diagram
-
-
-
-
-
1,3-Diphosphoglycerate
2,3-Diphosphoglycerate
show the reaction diagram
-
-
-
-
-
1,3-Diphosphoglycerate
2,3-Diphosphoglycerate
show the reaction diagram
-
-
-
-
-
1,3-Diphosphoglycerate
2,3-Diphosphoglycerate
show the reaction diagram
-
-
-
-
?
1,3-Diphosphoglycerate
2,3-Diphosphoglycerate
show the reaction diagram
-
the enzyme has additional activities of EC 5.4.2.1(phosphoglycerate mutase) and EC 3.1.3.13 (bisphosphoglycerate phosphatase)
-
-
1,3-Diphosphoglycerate
2,3-Diphosphoglycerate
show the reaction diagram
-
the enzyme has additional activities of EC 5.4.2.1(phosphoglycerate mutase) and EC 3.1.3.13 (bisphosphoglycerate phosphatase)
-
-
-
1,3-Diphosphoglycerate
2,3-Diphosphoglycerate
show the reaction diagram
-
multifunctional enzyme for synthesis and degradation of 2,3-diphosphoglycerate
-
-
-
2,3-Diphosphoglycerate
?
show the reaction diagram
-
multifunctional enzyme for synthesis and degradation of 2,3-diphosphoglycerte, additional activities are diphosphoglycerate phosphatase and phosphoglycerate mutase
-
-
-
2,3-Diphosphoglycerate
?
show the reaction diagram
-
in red blood cells 2,3-diphosphoglycerate is the main allosteric effector of hemoglobin, shifting the equilibrium between the oxy and deoxy conformations of hemoglobin preferentially stabilizing the unliganded form. 2,3-Diphosphoglycerate also promotes the polymerization of deoxyhemoglobin in sickle cell disease
-
-
-
3-phospho-D-glyceroyl phosphate
2,3-bisphospho-D-glycerate
show the reaction diagram
-
-
-
-
?
3-phospho-D-glyceroyl phosphate
2,3-bisphospho-D-glycerate
show the reaction diagram
-
-
-
?
3-phospho-D-glyceroyl phosphate
2,3-bisphospho-D-glycerate
show the reaction diagram
-
-
-
-
?
3-phospho-D-glyceroyl phosphate
2,3-bisphospho-D-glycerate
show the reaction diagram
P07738
-
-
-
?
3-phospho-D-glyceroyl phosphate
2,3-bisphospho-D-glycerate
show the reaction diagram
-
-
-
-
?
3-phospho-D-glyceroyl phosphate
2,3-bisphospho-D-glycerate
show the reaction diagram
-
BPGM plays a pivotal role in the dissociation of oxygen from hemoglobin via 2,3-bisphospho-D-glycerate
-
?
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
2,3-Diphosphoglycerate
?
show the reaction diagram
-
multifunctional enzyme for synthesis and degradation of 2,3-diphosphoglycerte, additional activities are diphosphoglycerate phosphatase and phosphoglycerate mutase
-
-
-
2,3-Diphosphoglycerate
?
show the reaction diagram
-
in red blood cells 2,3-diphosphoglycerate is the main allosteric effector of hemoglobin, shifting the equilibrium between the oxy and deoxy conformations of hemoglobin preferentially stabilizing the unliganded form. 2,3-Diphosphoglycerate also promotes the polymerization of deoxyhemoglobin in sickle cell disease
-
-
-
3-phospho-D-glyceroyl phosphate
2,3-bisphospho-D-glycerate
show the reaction diagram
-
-
-
-
?
3-phospho-D-glyceroyl phosphate
2,3-bisphospho-D-glycerate
show the reaction diagram
-
-
-
-
?
3-phospho-D-glyceroyl phosphate
2,3-bisphospho-D-glycerate
show the reaction diagram
P07738
-
-
-
?
3-phospho-D-glyceroyl phosphate
2,3-bisphospho-D-glycerate
show the reaction diagram
-
-
-
-
?
3-phospho-D-glyceroyl phosphate
2,3-bisphospho-D-glycerate
show the reaction diagram
-
BPGM plays a pivotal role in the dissociation of oxygen from hemoglobin via 2,3-bisphospho-D-glycerate
-
?
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Na2S2O4
-
stimulation
NaHSO3
-
stimulation
additional information
-
phosphoprotein, 1 mol per mol of subunit covalently bound, phosphoryl-group stable at alkaline pH, but liberated from the denatured protein at acidic pH
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2,3-diphosphoglycerate
-
product inhibition
2,4,6-Trinitrobenzenesulfonate
-
-
2,4,6-Trinitrobenzenesulfonate
-
-
2,4,6-Trinitrobenzenesulfonate
-
amino-specific reagent, protection by 2,3-diphosphoglycerate or 1,3-diphosphoglycerate
2-phosphoglycerate
-
-
2-Phosphoglycolate
-
-
3-phosphoglycerate
-
-
CH3COO-
-
-
diphosphate
-
-
iodoacetamide
-
60% inhibition, protection by 2,3-diphosphoglycerate; protection by 2,3-diphosphoglycerate, or 3-phosphoglycerate, or 2-phosphoglycerate
N-ethylmaleimide
-
protection by 2,3-diphosphoglycerate, not by 3-phosphoglycerate or 2-phosphoglycerate
N-ethylmaleimide
-
-
Phytic acid
-
i.e. inositol hexaphosphate
potassium phosphate
-
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2-phosphoglycerate
-
required, can be substituted by 3-phosphoglycerate
2-Phosphoglycolate
-
0.02 mM activates
3-phosphoglycerate
-
required, can be substituted by 2-phosphoglycerate
phosphoenolpyruvate
-
stimulation
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0005
-
1,3-diphosphoglycerate
-
pH 7.5, low salt concentration
0.0007
-
1,3-diphosphoglycerate
-
pH 7.8
0.003
-
1,3-diphosphoglycerate
-
pH 7.2, 0.1 M KCl
0.0031
-
1,3-diphosphoglycerate
-
pH 7.2
0.0036
-
1,3-diphosphoglycerate
-
pH 6.8
0.0024
-
2,3-diphosphoglycerate
-
presence of activator 2-phosphoglycolate
0.0028
-
2,3-diphosphoglycerate
-
absence of activator 2-phosphoglycolate
0.0094
-
2,3-diphosphoglycerate
-
peak II enzyme
0.0096
-
2,3-diphosphoglycerate
-
peak I enzyme
0.0222
-
2,3-diphosphoglycerate
-
peak III enzyme
0.11
-
2,3-diphosphoglycerate
-
-
0.182
-
2,3-diphosphoglycerate
-
mutant S23G
0.281
-
2,3-diphosphoglycerate
-
mutant C22S
0.3
-
2,3-diphosphoglycerate
-
wild-type
0.583
-
2,3-diphosphoglycerate
-
mutant C22T
additional information
-
additional information
-
kinetic parameters
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
3.6
-
1,3-diphosphoglycerate
-
4C
12.5
-
1,3-diphosphoglycerate
-
25C
23.4
-
1,3-diphosphoglycerate
-
37C
0.0037
-
2,3-diphosphoglycerate
-
wild-type
0.00623
-
2,3-diphosphoglycerate
-
mutant C22S
0.00845
-
2,3-diphosphoglycerate
-
mutant S23G
0.152
-
2,3-diphosphoglycerate
-
mutant C22T
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.56
-
-
-
0.978
-
-
-
5.61
-
-
-
10.1
-
-
-
15
-
-
BPMG purified from diabetic patients
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
placental labyrinthine trophoblast, located at the maternal-placental interface
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
30000
-
-
SDS-PAGE, mass spectrometry
54000
-
-
gel filtration
56500
-
-
gel filtration, sedimentation equilibrium centrifugation
60000
-
-
gel filtration
63000
-
-
sedimentation equilibrium centrifugation
120000
-
-
ultracentrifugation, cyanogen bromide cleavage, tryptic digestion
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
dimer
-
2 * 27200, SDS-PAGE
dimer
-
2 * 29000, SDS-PAGE
dimer
-
2 * 32000, SDS-PAGE
dimer
-
2 * 26500, SDS-PAGE
dimer
-
2 * 30000, crystal structure, SDS-PAGE
tetramer
-
4 * 28000, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
glycoprotein
-
glycosylation at L158 leads to inactivation in diabetic patients
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
2.5 A, crystals have a rod-shaped morphology
-
co-crystallized with 2,3-bisphosphoglycerate. Enzyme conformation continuously changes during the different states of the reaction with in line phosphoryl transfer mechanism
-
hanging drop vapor diffusion method, using 18-22% (w/v) PEG 6K, 100 mM HEPES pH 6.8-7.2, at 17C
-
preliminary x-ray diffraction data
-
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
45
-
-
peak II enzyme stable, peak I and peak III enzyme 46% and 80% loss of activity in 10 min, respectively
55
-
-
stable for 60 min
55
-
-
mutant Arg89Cys unstable, protection by 0.5 mM 2,3-diphosphoglycerate or, to a lesser degree by 4 mM 3-phosphoglycerate or 2-phosphoglycerate
55
-
-
30 min stable
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-80C, precipitated with ammonium sulfate, 3 months stable
-
-20C, concentrated solutions or 4C, 5 mM glycylglycine, pH 7.5, 0.5 mM EDTA, 2.5 mg/ml bovine serum albumin, 2 months, 30% loss of activity
-
-80C stable for up to 1 month
-
-80C, sodium phosphate buffer, 20% glycerol
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
copurification of EC 5.4.2.1 (phosphoglycerate mutase) and EC 3.1.3.13 (bisphosphoglycerate phosphatase), three activities in one enzyme protein
-
copurification of EC 5.4.2.1 (phosphoglycerate mutase) and EC 3.1.3.13 (bisphosphoglycerate phosphatase), three activities in one enzyme protein
-
copurification of EC 5.4.2.1 (phosphoglycerate mutase) and EC 3.1.3.13 (bisphosphoglycerate phosphatase), three activities in one enzyme protein
-
expressed in Escherichia coli
-
mutant Arg89Cys
-
Ni-Speharose column chromatography
-
no bisphosphoglycerate phosphatase activity
-
purified from erythrocytes of diabetic patients
-
copurification of EC 5.4.2.1 (phosphoglycerate mutase) and EC 3.1.3.13 (bisphosphoglycerate phosphatase), three activities in one enzyme protein
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
-
expression in Escherichia coli
-
expression of wild-type and mutants in Escherichia coli
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression is about one third lower in placentae of insulin-like growth factor II heterozygote knockout mice compared to wild type
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
E89G
-
construction of mutants with shortened chains and a mutant with Arg89Gly or Arg89Ser
additional information
-
construction of variants by site directed mutagenesis replacing Ser23 and Cys22
additional information
-
a minimal deletion of 7 amino acids from the C-terminus completely abolishes all catalytic activities
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
BPGM deficiency can cause erythrocytosis