Information on EC 3.5.1.38 - glutamin-(asparagin-)ase

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

EC NUMBER
COMMENTARY hide
3.5.1.38
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RECOMMENDED NAME
GeneOntology No.
glutamin-(asparagin-)ase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
L-glutamine + H2O = L-glutamate + NH3
show the reaction diagram
L-asparagine is hydrolysed at 0.8 of the rate of L-glutamine, the D-isomers are also hydrolysed, but more slowly
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
carboxylic acid amide hydrolysis
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
L-asparagine degradation I
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L-asparagine degradation III (mammalian)
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L-citrulline biosynthesis
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L-glutamine degradation I
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superpathway of L-aspartate and L-asparagine biosynthesis
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aspartate and asparagine metabolism
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glutamate and glutamine metabolism
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Arginine biosynthesis
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Alanine, aspartate and glutamate metabolism
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D-Glutamine and D-glutamate metabolism
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Metabolic pathways
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Biosynthesis of secondary metabolites
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SYSTEMATIC NAME
IUBMB Comments
L-glutamine(L-asparagine) amidohydrolase
The enzyme from the bacterium Achromobacter hydrolyses L-asparagine at 0.8 of the rate of L-glutamine; the D-isomers are also hydrolysed, but more slowly. cf. EC 3.5.1.2, glutaminase and EC 3.5.1.1, asparaginase.
CAS REGISTRY NUMBER
COMMENTARY hide
39335-03-0
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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Manually annotated by BRENDA team
highest activity in 4 days old nitrate-grown mats; NRRL3
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Manually annotated by BRENDA team
highest activity in 4 days old nitrate-grown mats; NRRL3
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Manually annotated by BRENDA team
3 forms: asparaginase-glutaminase, asparaginase A, asparaginase B
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Manually annotated by BRENDA team
; nitrate-grown mat
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Manually annotated by BRENDA team
; nitrate-grown mat
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Manually annotated by BRENDA team
Tilachlidium humicola
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Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
5-diazo-4-oxo-L-norvaline + H2O
?
show the reaction diagram
aspartic acid + H2O
?
show the reaction diagram
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very low activity only for asparaginase B
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-
?
beta-cyanoalanine + H2O
alanine + NH3
show the reaction diagram
beta-D-aspartyl hydroxylammonium sulfate + H2O
L-Asp + hydroxylammonium sulfate
show the reaction diagram
beta-L-aspartyl hydroxylammonium sulfate + H2O
L-Asp + hydroxylammonium sulfate
show the reaction diagram
D-asparagine + H2O
D-aspartate + NH3
show the reaction diagram
D-glutamine + H2O
D-glutamate + NH3
show the reaction diagram
gamma-L-glutamyl hydroxylammonium sulfate + H2O
L-glutamate + hydroxylammonium sulfate
show the reaction diagram
L-asparagine + H2O
L-aspartate + NH3
show the reaction diagram
L-glutamine + H2O
L-glutamate + NH3
show the reaction diagram
N-acetyl-L-asparagine + H2O
N-acetyl-L-aspartate + NH3
show the reaction diagram
N-carbamoyl-L-asparagine + H2O
N-carbamoyl-L-aspartate + NH3
show the reaction diagram
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-
?
N-glycyl-L-asparagine + H2O
N-glycyl-L-aspartate + NH3
show the reaction diagram
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60% higher activity than on L-asparagine
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?
succinamic acid + H2O
succinate + NH3
show the reaction diagram
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slow hydrolysis rate
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?
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
L-asparagine + H2O
L-aspartate + NH3
show the reaction diagram
L-glutamine + H2O
L-glutamate + NH3
show the reaction diagram
additional information
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Fe3+
Tilachlidium humicola
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30% activation at 1 mM
Ni2+
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slightly enhanced activity
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(NH4)2SO4
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inhibition above 10 mM
2-Hydroxy-5-nitrobenzyl bromide
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40% inhibition at 10 mM, concentration-dependent, protection against inhibition in presence of substrate
5-diazo-4-oxo-D-norvaline
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40% inhibition at 2 mM
5-Diazo-4-oxo-L-norvaline
6-diazo-5-oxo-L-norleucine
acivicin
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competitive inhibition
aspartic acid
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competitive inhibition, Ki: glutaminase activity 0.16 mM, asparaginase activity 0.53 mM
azaserine
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competitive not reversible inhibition of both activities
Bromocresol green
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52-66% inhibition at 1 mM
Cu2+
Tilachlidium humicola
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slight inhibition at 1 mM
D-asparagine
Tilachlidium humicola
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mixed type of competitive and non-competitive inhibition, Ki: 7.2-8.4 mM
EDTA
Tilachlidium humicola
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slight inhibition at 8 mM
glutamic acid
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competitive inhibition, Ki: glutaminase acitvity 5 mM, asparaginase activity 3 mM
iodoacetamide
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slight inhibition
KCN
Tilachlidium humicola
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slight inhibition at 8 mM
L-asparagine
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competitive inhibition of glutaminase activity, Ki: 0.02 mM
L-methionine sulfoximine
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competitive inhibition
N-bromosuccinimide
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concentration-dependent inhibition, 40% at 10 mM, protection against inhibition in presence of substrate
NaAsO2
Tilachlidium humicola
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90% inhibition at 8 mM
NaF
Tilachlidium humicola
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slight inhibition at 8 mM
NH4Cl
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weak non-competitive inhibition of glutaminase activity
Ni2+
Tilachlidium humicola
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33% inhibition at 1 mM
p-chloromercuribenzoate
Urea
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95% loss of activity in 2.25 M
additional information
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no product inhibition
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-mercaptoethanol
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slight activation
cysteine
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slight activation
dithiothreitol
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slight activation
additional information
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use of phosphate buffer yields higher activities than Tris, phthalate, or citrate buffer, optimum concentration is 0.08 - 0.16 M phosphate
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0026 - 2.57
L-asparagine
0.002 - 6.45
L-glutamine
10
N-acetyl-L-asparagine
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8
N-carbamoyl-L-asparagine
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2.4
N-glycyl-L-asparagine
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.6
5-Diazo-4-oxo-L-norvaline
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7.2 - 8.4
D-asparagine
Tilachlidium humicola
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mixed type of competitive and non-competitive inhibition
0.02
L-asparagine
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competitive inhibition of glutaminase activity
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
1.6
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asparaginase B
17.2
Tilachlidium humicola
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86
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asparaginase activity
100
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for L-asparagine
104
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glutaminase activity
133
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asparaginase A
2156
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glutaminase activity
10510
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asparaginase activity
additional information
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intracellular amino acid levels of wild-type and mutant strains
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4
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activity is higher in phosphate buffer than in citrate buffer
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 7
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optimal range for asparaginase activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37 - 55
Tilachlidium humicola
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
Tilachlidium humicola
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Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
Pseudomonas sp. (strain ATCC 29598 / 7A)
Pseudomonas sp. (strain ATCC 29598 / 7A)
Pseudomonas sp. (strain ATCC 29598 / 7A)
Pseudomonas sp. (strain ATCC 29598 / 7A)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
36000
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4 * 36000, sedimentation equilibrium analysis in the presence of guanidine HCl, amino acid analysis
39000
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4 * 39000, SDS-PAGE
87000
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2 * 87000, SDS-PAGE
132000 - 138000
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sedimentation equilibrium analysis
140000
156000
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gel filtration
180000
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gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
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2 * 87000, SDS-PAGE
tetramer
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method, single subunit, 2 A resolution
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hanging drop vapor diffusion method, in presence of inhibitors
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molecular replacement method, 1.7 A resolution
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molecular replacement method, 2.0 A resolution, 20-residue loop as part of the active site
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7
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complete inactivation
209094
7.2
Tilachlidium humicola
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less stable than at pH 5.6 or pH 10
209101
7.4
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70% activity
209097
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
Tilachlidium humicola
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stable within 16 h between pH 4-10
40
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30 min, about 10% loss of activity
51
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asparaginase B, half-life: 10 min
60
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30 min, about 70% loss of activity; incubation at 60C in the absence of substrate for 20 min causes a 70% increase in activity
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
stabilizing effect by addition of glycine and maintaining the pH to 9.0
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stabilizing effect during purification by sodium glutamate
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-10C, lyophilized to dryness in the presence of 50 mM Tris, 250 mM glycine, pH 9.0, 90% activity in 3 months
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4C, 12 months, asparaginase A, asparaginase B: DTT required, 6 months
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4C, 50 mM borate buffer, pH 7.0, 100 mM NaCl, 1 mM EDTA, 3 to 4 months
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activity is retained in the freezer for some months
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
near homogeneity, recombinant enzyme
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partial
Tilachlidium humicola
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to crystalline form, 3step chromatography
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to homogeneity
to homogeneity, 3step chromatography
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to homogeneity, asparaginase A
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to homogeneity, chromatography, preparative gel electrophoresis
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to homogeneity, improved purification by treatment with protamine sulfate, heating in the presence of stabilizer sodium glutamate
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to homogeneous crystals
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
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