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
LITERATURE
3-phospho-D-glyceroyl phosphate = 2,3-bisphospho-D-glycerate
show the reaction diagram
mechanism
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
group transfer
-
-
intramolecular, phosphate group
-
isomerization
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Glycolysis / Gluconeogenesis
-
-
Metabolic pathways
-
-
Rapoport-Luebering glycolytic shunt
-
-
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
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
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
-
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
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
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
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
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
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
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-
-
-
Cl-
-
-
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
-
-
NaHSO3
-
-
Phytic acid
-
i.e. inositol hexaphosphate
potassium phosphate
-
-
SO42-
-
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
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]
SUBSTRATE
ORGANISM
UNIPROT
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]
SUBSTRATE
ORGANISM
UNIPROT
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]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.56
-
-
0.978
-
-
5.61
-
-
10.1
-
-
15
-
BPMG purified from diabetic patients
additional information
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
placental labyrinthine trophoblast, located at the maternal-placental interface
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30000
-
SDS-PAGE, mass spectrometry
662264
54000
-
gel filtration
3255
56500
-
gel filtration, sedimentation equilibrium centrifugation
3321
60000
-
gel filtration
3313, 3319, 3320
63000
-
sedimentation equilibrium centrifugation
3319
120000
-
ultracentrifugation, cyanogen bromide cleavage, tryptic digestion
3257
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
-
2 * 32000, SDS-PAGE
dimer
-
2 * 29000, SDS-PAGE
dimer
-
2 * 27200, SDS-PAGE
dimer
-
2 * 26500, SDS-PAGE
dimer
-
2 * 30000, crystal structure, SDS-PAGE
tetramer
-
4 * 28000, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
-
glycosylation at L158 leads to inactivation in diabetic patients
Crystallization/COMMENTARY
ORGANISM
UNIPROT
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
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45
-
peak II enzyme stable, peak I and peak III enzyme 46% and 80% loss of activity in 10 min, respectively
3319
55
-
stable for 60 min
3307
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
3310
55
-
30 min stable
3326
STORAGE STABILITY
ORGANISM
UNIPROT
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
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
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
-
expression in Escherichia coli
-
expression of wild-type and mutants in Escherichia coli
-
EXPRESSION
ORGANISM
UNIPROT
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
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
COMMENTARY
LITERATURE
medicine
-
BPGM deficiency can cause erythrocytosis