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Information on EC 3.5.1.1 - asparaginase and Organism(s) Dickeya chrysanthemi and UniProt Accession P06608
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3.5.1.1 asparaginaseSpecify your search results
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- 3.5.1.1
- leukemia
- lymphoblastic
- children
-
remission
- erwinia
- hypersensitivity
- methotrexate
- lymphoma
- vincristine
-
pegylated
-
relapse
- pancreatitis
- thrombosis
- prednisone
-
high-dose
- venous
-
oncology
-
event-free
-
schedule
- cytarabine
-
consolidation
-
intensification
-
antileukemic
-
intrathecal
- antithrombin
-
l-aspartic
- chrysanthemi
- anthracyclines
- medicine
-
reinduction
- cyclophosphamide
-
pegaspargase
- thromboembolism
- allergy
- acrylamide
-
arabinoside
- mercaptopurine
- daunorubicin
- osteonecrosis
- analysis
-
philadelphia
-
extranodal
-
fried
-
b-precursor
- succinogenes
-
standard-risk
- synthesis
-
coli-derived
- food industry
- diagnostics
- biotechnology
-
dana-farber
- pharmacology
- teniposide
- carotovora
-
multiagent
The taxonomic range for the selected organisms is: Dickeya chrysanthemi
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
asparaginase, l-asnase, asrgl1, asparaginase ii, l-asparaginase ii, erwinase, ecaii, l-asparaginase i, ecaiii, diasp, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
alpha-asparaginase
-
-
-
-
asparaginase II
-
-
-
-
colaspase
-
-
-
-
crasnitin
-
-
-
-
DiAsp
-
-
-
-
elspar
-
-
-
-
L-ASNase
L-asparaginase
L-asparagine amidohydrolase
-
-
-
-
leunase
-
-
-
-
L-ASNase
-
-
-
-
L-asparaginase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
carboxylic acid amide hydrolysis
-
-
-
-
PATHWAY SOURCE
PATHWAYS
KEGG
-
-, -, -
SYSTEMATIC NAME
IUBMB Comments
L-asparagine amidohydrolase
-
CAS REGISTRY NUMBER
COMMENTARY
9015-68-3
-
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
N-acetyl-L-asparagine + H2O
N-acetyl-L-aspartic acid + NH3
-
-
-
?
L-asparagine + H2O
L-aspartate + NH3
-
the enzyme does not reduce alpha-antiplasmin and plasminogen levels in human patients with acute lymphoblastic leukemia
-
-
?
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
L-asparagine + H2O
L-aspartate + NH3
-
the enzyme does not reduce alpha-antiplasmin and plasminogen levels in human patients with acute lymphoblastic leukemia
-
-
?
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
wild-type and N281D enzymes have roughly the same pI, as do the N41D and the double mutant
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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). PDB
SCOP
CATH
UNIPROT
ORGANISM
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
complexed with the L- and D-stereoisomers of the suicide inhibitor L-6-diazo-5-oxy-norleucine and D-6-diazo-5-oxynorleucine solved using X-ray crystallography and refined with data extending to 1.7 A
crystal structures in complex with L-aspartic acid and with L-glutamic acid. The enzyme conformations open and closed correspond to the inactive and active states, respectively. The binding of ligands induces the positioning of the catalytic Thr15 into its active conformation, which in turn allows for the ordering and closure of the flexible N-terminal loop. L-Aspartic acid is more efficient than L-glutamic acid in inducing the active positioning of Thr15
high-resultion crystal structures of the complex of L-asparaginase with L-Glu, D-Asp and succinic acid
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D133I
analysis of the contribution of this position on thermostability
D133L
analysis of the contribution of this position on thermostability
D133T
analysis of the contribution of this position on thermostability
D133V
analysis of the contribution of this position on thermostability
N281D
-
mutant has approximately the same specific activity as the wild-type enzyme. Mutation results in a lower glutaminase activity compared with wild-type and the N41D mutant. Mutation imparts less stability to the enzyme at elevated temperatures. The N281D mutation causes a decrease in substrate affinity as well as a decrease in the stability profile. The deamidation at the N281 site should not be a concern during processing, storage or clinical use. The deamidated variant is active and stable under normal storage conditions
N41D
-
mutant has approximately the same specific activity as the wild-type enzyme. Mutation conferrs a slight increase in kcat. Charge differences to the wild-type enzyme, at -1 per monomer or -4 per tetramer. The deamidation at the N41 site should not be a concern during processing, storage or clinical use. These deamidated variant is active and stable under normal storage conditions
N41D/N281D
-
mutant enzyme has increased specific activity. Charge differences to the wild-type enzyme, at -1 per monomer or -4 per tetramer. The N281D mutation causes a decrease in substrate affinity as well as a decrease in the stability profile. The deamidation at the N41 and N281 sites should not be a concern during processing, storage or clinical use. These deamidated variant is active and stable under normal storage conditions
additional information
additional information
-
immobilization of the purified recombinant enzyme on epoxy-activated resin, the immobilized enzyme retains 60% of maximal activity and is highly stable at 4°C, utilization as bioreactor
additional information
immobilization of the purified recombinant enzyme on epoxy-activated resin, the immobilized enzyme retains 60% of maximal activity and is highly stable at 4°C, utilization as bioreactor
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
46
enzyme shows higher thermal stability at acidic to neutral pH values, lower stability is observed at alkaline pH. The inactivation profiles at pH 5.5 and 7 are biphasic and shows two clear transitions with inflection points corresponding to Tm values of 46.6°C and 62.5°C at pH 5.5, and 46.4 and 57.2°C at pH 7, respectively
47
enzyme shows higher thermal stability at acidic to neutral pH values, lower stability is observed at alkaline pH. The inactivation profiles at pH 5.5 and 7 are biphasic and shows two clear transitions with inflection points corresponding to Tm values of 46.6°C and 62.5°C at pH 5.5, and 46.4 and 57.2°C at pH 7, respectively
49
-
3 min, 50% loss of activity of mutant enzyme N281D and double mutant enzyme N41D/N281D, no loss of activity of wild-type enzyme and mutant enzyme N41D
50
55
57
enzyme shows higher thermal stability at acidic to neutral pH values, lower stability is observed at alkaline pH. The inactivation profiles at pH 5.5 and 7 are biphasic and shows two clear transitions with inflection points corresponding to Tm values of 46.6°C and 62.5°C at pH 5.5, and 46.4 and 57.2°C at pH 7, respectively
63
enzyme shows higher thermal stability at acidic to neutral pH values, lower stability is observed at alkaline pH. The inactivation profiles at pH 5.5 and 7 are biphasic and shows two clear transitions with inflection points corresponding to Tm values of 46.6°C and 62.5°C at pH 5.5, and 46.4 and 57.2°C at pH 7, respectively
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
the enzyme can be efficiently immobilized on epoxy-activated Sepharose CL-6B. The immobilized enzyme retains most of its activity (60%) and shows high stability at 4°C
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
urea
-
the N281D mutation results in an inability to refold after exposure to urea concentrations greater than 1.5 M, while the external N41D mutation has no impact on the stability of the enzyme
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme from Escherichia coli strain BL21(DE3) in a single step procedure to homogeneity by cation exchange
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
the enzyme is used for acute lymphoblastic leukemia treatment, the enzyme does not reduces alpha-antiplasmin and plasminogen levels in human patients, overview
medicine
the enzyme can be efficiently immobilized on epoxy-activated Sepharose CL-6B. The immobilized enzyme retains most of its activity (60%) and shows high stability at 4°C. The approach offers the possibility of designing an L-asparaginase from Erwinia chrysanthemi bioreactor that can be operated over a long period of time with high efficiency, which can be used in leukaemia therapy
medicine
-
the enzyme is an important biopharmaceutical product used in the treatment of acute lymphoblastic leukaemia
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Lubkowski, J.; Dauter, M.; Aghaiypour, K.; Wlodawer, A.; Dauter, Z.
Atomic resolution structure of Erwinia chrysanthemi L-asparaginase
Acta Crystallogr. Sect. D
59
84-92
2003
Dickeya chrysanthemi (P06608)
Aghaiypour, K.; Wlodawer, A.; Lubkowski, J.
Structural basis for the activity and substrate specificity of Erwinia chrysanthemi L-asparaginase
Biochemistry
40
5655-5664
2001
Dickeya chrysanthemi (P06608), Dickeya chrysanthemi
Aghaiypour, K.; Wlodawer, A.; Lubkowski, J.
Do bacterial L-asparaginases utilize a catalytic triad Thr-Tyr-Glu?
Biochim. Biophys. Acta
1550
117-128
2001
Dickeya chrysanthemi (P06608)
Appel, I.M.; Hop, W.C.; Pieters, R.
Changes in hypercoagulability by asparaginase: a randomized study between two asparaginases
Blood Coagul. Fibrinolysis
17
139-146
2006
Escherichia coli, Dickeya chrysanthemi
Kotzia, G.A.; Labrou, N.E.
L-Asparaginase from Erwinia chrysanthemi 3937: cloning, expression and characterization
J. Biotechnol.
127
657-669
2006
Dickeya chrysanthemi, Dickeya chrysanthemi (Q6Q4F3), Dickeya chrysanthemi 3937, Dickeya chrysanthemi 3937 (Q6Q4F3)
Kotzia, G.A.; Labrou, N.E.
Engineering thermal stability of L-asparaginase by in vitro directed evolution
FEBS J.
276
1750-1761
2009
Pectobacterium carotovorum, Dickeya chrysanthemi (Q6Q4F3), Dickeya chrysanthemi
Gervais, D.; Foote, N.
Recombinant deamidated mutants of Erwinia chrysanthemi L-asparaginase have similar or increased activity compared to wild-type enzyme
Mol. Biotechnol.
56
865-877
2014
Dickeya chrysanthemi, Dickeya chrysanthemi NCPPB 1066
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