Information on EC 3.4.22.40 - bleomycin hydrolase

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

EC NUMBER
COMMENTARY hide
3.4.22.40
-
RECOMMENDED NAME
GeneOntology No.
bleomycin hydrolase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
Inactivates bleomycin B2 (a cytotoxic glycometallopeptide) by hydrolysis of a carboxyamide bond of beta-aminoalanine, but also shows general aminopeptidase activity. The specificity varies somewhat with source, but amino acid arylamides of Met, Leu and Ala are preferred
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
53096-17-6
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
chinese hamster
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
baboon
-
-
Manually annotated by BRENDA team
bullfrog
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
-
bleomycin hydrolase protects against L-homocysteine-thiolactone toxicity in brain and kidney
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
Ala-p-nitroanilide + H2O
Ala + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
amyloid peptide Abeta1-40 + H2O
peptide fragments
show the reaction diagram
-
processing by cleavage at bonds His14-Gln15 and Phe19-Phe20, endopeptidase activity, substrate preparation, overview
product determination by MALDI-TOF mass spectrometry
-
?
amyloid peptide Abeta1-42 + H2O
peptide fragments
show the reaction diagram
-
processing by cleavage at bonds His14-Gln15 and Phe19-Phe20, endopeptidase activity, substrate preparation, overview
product determination by MALDI-TOF mass spectrometry
-
?
amyloid peptide Abeta3-42 + H2O
?
show the reaction diagram
-
processing
-
-
?
Arg-p-nitroanilide + H2O
Arg + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
Asp-p-nitroanilide + H2O
Asp + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
bleomycin + H2O
?
show the reaction diagram
bleomycin + H2O
deamido-bleomycin
show the reaction diagram
bleomycin A2 + H2O
?
show the reaction diagram
bleomycin B2 + H2O
?
show the reaction diagram
bleomycinic acid + H2O
?
show the reaction diagram
-
-
-
-
?
butylamino-3-propylamino-3-propylamine bleomycin + H2O
?
show the reaction diagram
-
-
-
-
?
citrulline-4-methylcoumarin 7-amide + H2O
citrulline + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
citrulline-7-amido-4-methylcoumarin + H2O
citrulline + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
citrulline-beta-naphthylamide + H2O
citrulline + beta-naphthylamine
show the reaction diagram
deglyco bleomycin A2 + H2O
?
show the reaction diagram
-
-
-
-
?
deiminated filaggrin + H2O
?
show the reaction diagram
Glu-4-methylcoumarin 7-amide + H2O
Glu + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
Gly-Ala + H2O
Gly + Ala
show the reaction diagram
-
-
-
-
?
Gly-Asp + H2O
Gly + Asp
show the reaction diagram
-
-
-
-
?
Gly-D-Leu + H2O
Gly + D-Leu
show the reaction diagram
-
-
-
-
?
Gly-Gly + H2O
?
show the reaction diagram
-
-
-
-
?
Gly-Gly-Ala + H2O
glycyl-L-alanine + glycine
show the reaction diagram
-
-
-
-
?
Gly-Gly-Arg + H2O
?
show the reaction diagram
-
-
-
-
?
Gly-Gly-D-Leu + H2O
?
show the reaction diagram
-
-
-
-
?
Gly-Gly-Glu + H2O
?
show the reaction diagram
-
-
-
-
?
Gly-Gly-Gly-Ala + H2O
?
show the reaction diagram
-
-
-
-
?
Gly-Gly-Gly-Gly + H2O
?
show the reaction diagram
-
-
-
-
?
Gly-Gly-Gly-Gly-Gly + H2O
?
show the reaction diagram
-
-
-
-
?
Gly-Gly-Leu + H2O
?
show the reaction diagram
-
-
-
-
?
Gly-Gly-NH2 + H2O
?
show the reaction diagram
-
-
-
-
?
Gly-Gly-Phe + H2O
?
show the reaction diagram
-
-
-
-
?
Gly-Gly-Phe-Leu + H2O
?
show the reaction diagram
-
-
-
-
?
Gly-Gly-Tyr + H2O
?
show the reaction diagram
-
-
-
-
?
Gly-Leu + H2O
Gly + Leu
show the reaction diagram
-
-
-
-
?
Gly-Lys + H2O
Gly + Lys
show the reaction diagram
-
-
-
-
?
Gly-NH2 + H2O
Gly + NH3
show the reaction diagram
-
-
-
-
?
Gly-p-nitroanilide + H2O
Gly + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
Gly-Phe + H2O
Gly + Phe
show the reaction diagram
-
-
-
-
?
homocysteine-thiolactone + H2O
?
show the reaction diagram
-
-
-
-
?
huntingtin + H2O
?
show the reaction diagram
-
the enzyme is involved in a specific cleavage step at the N-terminal fragment cp-2 site of huntingtin
-
-
?
L-Arg-7-amido-4-methylcoumarin + H2O
L-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
protease activity of mutant variants determined using substrate concentrations ranging from 0 to 0.125 mM
-
-
?
L-homocysteine-thiolactone + H2O
L-homocysteine
show the reaction diagram
-
-
-
-
?
L-tyrosine-p-nitroanilide + H2O
L-tyrosine + 4-nitroaniline
show the reaction diagram
72% of activity with phenylalanine-betanitroanilide
-
?
Leu-p-nitroanilide + H2O
Leu + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
Lys-p-nitroanilide + H2O
Lys + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
Met-Ala + H2O
Met + Ala
show the reaction diagram
-
-
-
-
?
Met-Ala-Ser + H2O
?
show the reaction diagram
-
-
-
-
?
Met-p-itroanilide + H2O
Met + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
peplomycin + H2O
?
show the reaction diagram
-
-
-
-
?
Phe-p-nitroanilide + H2O
Phe + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
phenylalanine-betanaphthylamide + H2O
beta-naphthylamin + phenylalanine
show the reaction diagram
best substrate
-
?
phenylalanine-p-nitroanilide + H2O
p-nitroaniline + phenylalanine
show the reaction diagram
activity comparable to phenylalanine-betanitroanilide
-
?
tallysomycin S10b + H2O
?
show the reaction diagram
-
-
-
-
?
Thr-Ser + H2O
Thr + Ser
show the reaction diagram
-
-
-
-
?
Thr-Ser-Lys + H2O
?
show the reaction diagram
-
-
-
-
?
Z-Leu-Leu-Glu-NH-4-nitroanilide + H2O
Z-Leu-Leu-Glu + 4-nitroaniline
show the reaction diagram
-
no activity in vitro due to requirement of binding to DNA-recognition sites of ztranscriptional activator Gal4p
-
-
?
additional information
?
-
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
bleomycin + H2O
?
show the reaction diagram
deiminated filaggrin + H2O
?
show the reaction diagram
homocysteine-thiolactone + H2O
?
show the reaction diagram
-
-
-
-
?
huntingtin + H2O
?
show the reaction diagram
-
the enzyme is involved in a specific cleavage step at the N-terminal fragment cp-2 site of huntingtin
-
-
?
L-homocysteine-thiolactone + H2O
L-homocysteine
show the reaction diagram
-
-
-
-
?
Z-Leu-Leu-Glu-NH-4-nitroanilide + H2O
Z-Leu-Leu-Glu + 4-nitroaniline
show the reaction diagram
-
no activity in vitro due to requirement of binding to DNA-recognition sites of ztranscriptional activator Gal4p
-
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
glycometalloenzyme
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1-(L-trans-epoxysuccinylleucylamino)-4-guanidinobutane
4-hydroxymeruribenzoate
Arg-Ala
-
86% inhibition of HLTase activity at 2 mM
H2O2
-
41% inhibition of HLTase activity 2 mM
iodoacetamide
iodoacetate
Leu-Ala
-
50% inhibition of HLTase activity at 2 mM
leupeptin
Lys-Ala
-
77% inhibition of HLTase activity at 2 mM
Lys-Leu
-
26% inhibition of HLTase activity at 2 mM
N-ethylmaleimide
-
-
p-tosyl-L-lysine chloromethyl ketone
-
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
dithiothreitol
-
activates
galactose
-
transcripton regulator
Nucleic acids
-
RNA, single-stranded DNA or nicked DNA are bound
-
additional information
-
binding to nucleic acids, preferably single-stranded DNA or RNA, is required for enzyme activity
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
17.4
Ala-p-nitroanilide
-
-
6.1
Arg-p-nitroanilide
-
-
28.4
Asp-p-nitroanilide
-
-
0.46 - 1.3
bleomycin A2
0.056 - 0.79
bleomycin B2
2.25
butylamino-3-propylamino-3-propylamine bleomycin
-
-
-
0.49
deglyco bleomycin A2
-
-
2.9
Gly-Ala
-
-
14.8
Gly-Asp
-
-
5.6
Gly-D-Leu
-
-
10.1
Gly-Gly
-
-
0.66
Gly-Gly-Ala
-
-
0.75
Gly-Gly-Arg
-
-
1.01
Gly-Gly-D-Leu
-
-
1.14
Gly-Gly-Glu
-
-
1.05
Gly-Gly-Gly
-
-
0.13
Gly-Gly-Gly-Ala
-
-
0.78 - 1.24
Gly-Gly-Gly-Gly
0.57
Gly-Gly-Leu
-
-
4.1
Gly-Gly-NH2
-
-
0.29
Gly-Gly-Phe
-
-
0.2
Gly-Gly-Phe-Leu
-
-
1.05
Gly-Gly-Tyr
-
-
4.6
Gly-Leu
-
-
4.7
Gly-Lys
-
-
13.5
Gly-NH2
-
-
9.7
Gly-p-nitroanilide
-
-
1.7
Gly-Phe
-
-
12.5
Leu-p-nitroanilide
-
-
9.9
Lys-p-nitroanilide
-
-
9.5
Met-Ala
-
-
0.5
Met-Ala-Ser
-
-
7
Met-paranitroanilide
-
-
0.7 - 0.79
peplomycin
3.5
Phe-p-nitroanilide
-
-
0.45
tallysomycin S10b
-
-
2.7
Thr-Ser
-
-
0.63
Thr-Ser-Lys
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
189
pH 5.2, 30°C
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 8
stable for 90 min
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
high expression level
Manually annotated by BRENDA team
histological examination, increase in GFAP-positively stained astroglia observed in the brains of aged null mice compared with wild-type controls
Manually annotated by BRENDA team
MEFs, bleomycin hydrolase-deficient cells from mice
Manually annotated by BRENDA team
extracts, bleomycin hydrolase detection by Western blot
Manually annotated by BRENDA team
testicular germ-cell cancer, response to chemotherapy dependent on gene polymorphism of bleomycin hydrolase analyzed
Manually annotated by BRENDA team
detected by immunohistochemistry
Manually annotated by BRENDA team
of 6-week-old rats, tissue amounts of bleomycin hydrolase determined, relative high amounts detected
Manually annotated by BRENDA team
-
high expression level
Manually annotated by BRENDA team
leukocyte-rich cell extracts, detection by Western blot
Manually annotated by BRENDA team
bleomycin hydrolase detected by immunohistochemistry
Manually annotated by BRENDA team
of 6-week-old rats, tissue amounts of bleomycin hydrolase determined
Manually annotated by BRENDA team
hemo-lymphocytic lineage cell line, bleomycin hydrolase detection by Western blot
Manually annotated by BRENDA team
of 6-week-old rats, tissue amounts of bleomycin hydrolase determined
Manually annotated by BRENDA team
of 6-week-old rats, red pulpy region, detected by immunohistochemistry
Manually annotated by BRENDA team
of 6-week-old rats, tissue amounts of bleomycin hydrolase determined
Manually annotated by BRENDA team
6-week-old male rats, tissue amounts of bleomycin hydrolase determined
Manually annotated by BRENDA team
6-week-old female rats, tissue amounts of bleomycin hydrolase determined
Manually annotated by BRENDA team
additional information
-
no expression in Hodgkin's lymphoma cells
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
in the presence of Ca2+
-
Manually annotated by BRENDA team
-
colocalization of enzyme with amyloid precursor protein
Manually annotated by BRENDA team
outer membrane of, kidney epithel; outer membrane of, liver hepatocytes
Manually annotated by BRENDA team
additional information
PDB
SCOP
CATH
ORGANISM
UNIPROT
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
50000
-
5 * 50000, SDS-PAGE
72000
x * 72000, SDS-PAGE and deduced from gene sequence
250000
-
gel filtration, PAGE
280000
300000
310000
-
gel filtration
400000
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hexamer
octamer
-
8 * 52000, SDS-PAGE
pentamer
-
5 * 50000, SDS-PAGE
additional information
-
trypsin-mediated peptide mapping, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
-
glycometalloenzyme
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hanging-drop method, structure and catalytic site of yeast bleomycin hydrolase indicated, structural changes at the active site of mutant variants shown, data collection, refinements and structural alignments between wild-type and mutant variants indicated
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
loss of 50% activity after 10 h
50
1 h, pH 7.0, stable
60
1 h, pH 7.0, 5% residual activity
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
stabilized by 2 mM dithiothreitol
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli
-
gel filtration, SDS-PAGE
native enzyme 4300fold from newborn rat epidermis by gel filtration, and two steps of anion exchange chromatography
native enzyme from epidermis of newborn rats
-
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography to homogeneity
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
determination of DNA sequence and genotypes in 340 different male germ cell probes
-
DNA sequence determination
DNA sequence determination and analysis, chromosome localization at 19q11.2
-
expressed in Escherichia coli
expressed in Escherichia coli, mutant generation described
expressed in HT-22 cells
-
expression in CHO-K1 cells
-
expression in COS7 cells
-
expression in Escherichia coli
-
expression in Sf9/baculovirus cells
-
expression of His-tagged enzyme in Escherichia coli strain BL21(DE3)
gene YCP1 or BLH1, DNA sequence determination
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
bleomycin hydrolase expression is up-regulated via IRF-1/2, MZF-1 and Sp-1. mRNA is up-regulated in keratinocytes when cultured at high calcium concentration (6.8fold)
-
interferon-gamma significantly reduces the expression of bleomycin hydrolase. The enzyme activity and expression are markedly decreased in atopic dermatitis lesional and non-lesional skin (to 27.1 and 8.8%, respectively)
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interleukin-4 does not show any direct effect on bleomycin hydrolase expression
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C73A
-
inactive mutant
C73S
-
ectopic expression of enzyme increases the secretion of amyloid precursor protein, increase is blocked in mutant
truncated C-terminus
-
C-terminus is essential for protection against bleomycin induced chromatin breaks
V443I
-
the naturally occurring polymorphism of the gene encoding the enzyme is associated to sporadic Alzheimer's disease and to the amyloid precursor protein
H369L
structural and catalytic effects of mutations shown
N392A
structural and catalytic effects of mutations summarized
N392L
structural and catalytic effects of mutations shown
N392V
structural and catalytic effects of mutations shown
Q67E
structural and catalytic effects of mutations indicated
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
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