Information on EC 3.5.4.6 - AMP deaminase

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The expected taxonomic range for this enzyme is: Eukaryota

EC NUMBER
COMMENTARY hide
3.5.4.6
-
RECOMMENDED NAME
GeneOntology No.
AMP deaminase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
AMP + H2O = IMP + NH3
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
amidine hydrolysis
-
-
-
-
Deamination
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
adenosine nucleotides degradation I
-
-
Biosynthesis of antibiotics
-
-
Biosynthesis of secondary metabolites
-
-
Metabolic pathways
-
-
purine metabolism
-
-
Purine metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
AMP aminohydrolase
cf. EC 3.5.4.17 adenosine-phosphate deaminase.
CAS REGISTRY NUMBER
COMMENTARY hide
9025-10-9
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
goldfish
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
rainbow trout
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
pea
-
-
Manually annotated by BRENDA team
skate
-
-
Manually annotated by BRENDA team
also known as Lithobates sylvaticus
-
-
Manually annotated by BRENDA team
strain JM1901
-
-
Manually annotated by BRENDA team
strain 972
-
-
Manually annotated by BRENDA team
strain 972
-
-
Manually annotated by BRENDA team
corb
-
-
Manually annotated by BRENDA team
sea scorpion
-
-
Manually annotated by BRENDA team
spinach
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
AMP deaminase 3 is mutated in one of the mutant clones resistant to anthrax lethal toxin-induced death, AMPD3 deficiency does not affect anthrax lethal toxin entering cells and the cleavage of mitogen-activated protein kinase kinase by lethal factor inside cells, but does impair a downstream event that is linked to cell death. Restoration of anthrax lethal toxin sensitivity with ectopic reconstitution of AMPD3 expression
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2',3'-isopropylidene adenosine + H2O
2',3'-O-(1-methylethylidene)inosine + NH3
show the reaction diagram
-
low activity
-
-
?
5'-AMP + H2O
IMP + NH3
show the reaction diagram
-
-
-
-
?
5-deoxyadenylic acid + H2O
dIMP + NH3
show the reaction diagram
adenosine + H2O
inosine + NH3
show the reaction diagram
-
the activity of AMPDA with adenosine is not influenced by variation of pH values between 4 and 7, the highest activity is at pH 8
-
-
?
adenosine 5'-monosulfate + H2O
inosine 5'-monosulfate + NH3
show the reaction diagram
-
-
-
-
?
adenosine phosphoramidate + H2O
?
show the reaction diagram
-
-
-
-
?
AMP + H2O
IMP + NH3
show the reaction diagram
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
AMP + H2O
IMP + NH3
show the reaction diagram
additional information
?
-
-
key enzyme of nucleotide breakdown is involved in regulation of adenine nucleotide pool in the liver
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Cs+
-
activates
Li+
-
activates
Mg2+
-
activates
NaCl
-
100-150 mM activates
Rb+
-
activates
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(S)-2-(4-bromo-biphenyl-4-sulfonyl)amino-3-methyl butyric acid
-
i.e. PD166793
1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopenta-gamma-2-benzopyran
-
IC50: 0.0003 mM
1-(5,6,7,8-tetrahydro)3,5,5,6,8,8-hexamethyl-2-naphthalenyl-ethanone
-
IC50: 0.0003 mM
1-bromo-4-[2-(8-hydroxy-7,8-dihydroimidazo[4,5-d][1,3]diazepin-3(6H)-yl)ethyl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid
1-n-butyl-3-methylimidazolium chloride
-
IC50: 0.01 mM
1-n-butyl-3-methylimidazolium p-tosylate
-
IC50: 0.01 mM
1-n-butyl-3-methylimidazolium tetrafluoroborate
-
IC50: 0.005 mM
1-n-butyl-3-methylimidazolium tetrafluorophosphate
-
IC50: 0.005 mM
1-t-butyl-3,5-dimethyl-2,4,6-trinitrobenzene
-
IC50: 0.0003 mM
2'-AMP
-
in the absence of ATP
2,3-diphosphoglyceric acid
-
ATP counteracts inhibition
3'-AMP
-
in the absence of ATP
3-[2-(3-carboxy-4-bromo-5,6,7,8-tetrahydronaphthyl)ethyl]-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol
3-[2-(3-carboxy-5,6,7,8-tetrahydronaphthyl)-ethyl]imidazo[2,1-f][1,2,4]triazine
3-[2-(8-hydroxy-7,8-dihydroimidazo[4,5-d][1,3]diazepin-3(6H)-yl)ethyl]benzoic acid
3-[2-(imidazo[2,1-f][1,2,4]triazin-7-yl)ethyl]benzoic acid
4-acetyl-1-t-butyl-3,5-dimethyl-2,6-dinitrobenzene
-
IC50: 0.0005 mM
4-[2-(8-hydroxy-7,8-dihydroimidazo[4,5-d][1,3]diazepin-3(6H)-yl)ethyl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid
5'-IMP
5,5-dithio-bis(2-nitrobenzoic acid)
-
reaction with thiol groups, leads to a decrease of 20-30% in Vmax
adenine
-
0.25 mM
coformycin
coformycin 5'-phosphate
deaminoformycin
-
0.0003 mM, strong inhibitor
deaminoformycin 5'-monophosphate
-
potent inhibitor
diphosphate
-
-
fluoride
H2O2
-
treatment with 0.1 mM H2O2 reduces activity by half after about 50 min, 50% of activity is lost in about 25 min when AMPD is incubated with both iron and H2O2
IMP
-
uniquely inhibits only the bound (phosphorylated) enzyme from muscle of frozen frogs
iodoacetate
KCl
-
abover 150 mM
Leupeptin
-
-
N-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)pyridinium bromide
-
IC50: 0.05 mM
N-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)trimethylammonium bromide
-
IC50: 0.5 mM
p-hydroxymercuribenzoate
-
-
phenylmethane-sulfonylfluoride
-
-
phosphate
Protamine sulfate
-
-
-
purine riboside
-
prolonged exposure (60 min) to purine riboside results in AMPD inhibition
Tannic acid
-
above 0.004 mM, complete inactivation at 0.05 mM
trinitrobenzene sulfonic acid
-
regulatory function on activity and inhibition by other compounds, e.g. ATP, overview
additional information
-
incubation with 0.005 mM FeSO4 does not affect AMPD activity
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
adenine
-
activates
adenosine
Ca2+-calmodulin
-
-
-
Calmodulin
-
Ca2+-calmodulin activates erythrocyte AMPD in conditions of disturbed calcium homeostasis during sickle cell disease
citrate
-
activates
D-glucose
-
activates
dATP
-
activates
deoxyribose
-
activates
F-
-
slightly activates at concentrations up to 2 mM
glycerol
-
activates
GTP
-
activates
hypoxanthine
-
activates
native muscle proteinase
-
limited cleavage increases enzyme activity in presence of low concentrations of K+, probably due to removal of a fragment from the enzyme, which holds the enzyme in an inactive state, cleavage occurs e.g. during storage of both the muscle and the purified enzyme
-
phosphate
purine riboside
-
10 min perfusion of the pre-ischemic heart or incubation of cardiomyocytes with 0.2 mM purine riboside results in activation of AMPD
Trypsin
-
limited cleavage increases enzyme activity in presence of low concentrations of K+, probably due to removal of a fragment from the enzyme, which holds the enzyme in an inactive state
-
additional information
-
the percentage of bound AMPD activity increases from 20 to 35% with the transition to the frozen state
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.4 - 13
AMP
additional information
additional information
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000601
deaminoformycin 5'-monophosphate
-
in 25 mM imidazole, pH 6.5, 150 mM potassium chloride, 2.4 mM AMP, and 0.2 mg/ml bovine serum albumin
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0003
1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopenta-gamma-2-benzopyran
0.01
1-n-butyl-3-methylimidazolium chloride
0.005
1-n-butyl-3-methylimidazolium tetrafluoroborate
0.0003
1-t-butyl-3,5-dimethyl-2,4,6-trinitrobenzene
Rattus norvegicus
-
IC50: 0.0003 mM
0.5
3-[2-(3-carboxy-4-bromo-5,6,7,8-tetrahydronaphthyl)ethyl]-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol
Rattus norvegicus
-
-
0.0009 - 0.2
3-[2-(3-carboxy-5,6,7,8-tetrahydronaphthyl)-ethyl]imidazo[2,1-f][1,2,4]triazine
0.1 - 1.4
3-[2-(imidazo[2,1-f][1,2,4]triazin-7-yl)ethyl]benzoic acid
0.0005
4-acetyl-1-t-butyl-3,5-dimethyl-2,6-dinitrobenzene
Rattus norvegicus
-
IC50: 0.0005 mM
0.08 - 0.1
GTP
0.23
IMP
Rana sylvatica
-
myosin-bound AMPD from frozen skeletal muscle, in 50 mM MOPS buffer (pH 7.2), at 25C
162 - 702
K+
0.05
N-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)pyridinium bromide
Rattus norvegicus
-
IC50: 0.05 mM
0.5
N-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)trimethylammonium bromide
Rattus norvegicus
-
IC50: 0.5 mM
133 - 824
Na+
254
NH3
Rana sylvatica
-
free AMPD from frozen skeletal muscle, in 50 mM MOPS buffer (pH 7.2), at 25C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.008
-
-
0.01
-
enzyme from 40th week-old placenta, in 0.1 M succinate buffer, pH 6.5, at 5 mM substrate (AMP) concentration, at 30C
0.025
-
enzyme from 33rd week-old placenta, in 0.1 M succinate buffer, pH 6.5, at 5 mM substrate (AMP) concentration, at 30C
0.037
-
enzyme from 25th week-old placenta, in 0.1 M succinate buffer, pH 6.5, at 5 mM substrate (AMP) concentration, at 30C
0.077
-
non significant differences in enzyme activity are observed between homogenates from HCC tumor fragments and tumor surrounding fragments of the liver, where the specific activity is about 0.077 micromole/min/mg of protein
0.18 - 1.25
-
-
125
-
delta M90 AMPD3 mutant
865
-
wild-type AMPD3
900 - 1100
-
-
1100
-
purified enzyme
1850
-
wild-type AMPD1
2743
-
-
3112
-
DELTA L96 AMPD1 mutant
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.6 - 6.8
-
Tris-acetic acid buffer
6
-
enzyme from cirrhotic liver
6 - 6.2
-
succinate buffer
6.4
-
pH optimum about 6, depending on purification procedure and buffer
8
-
using adenosine as substrate
additional information
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 7.5
6 - 7.2
-
pH 6.0: about 55% of maximal activity, pH 7.2: about 55% of maximal activity, normal liver
additional information
-
AMP-deaminase from preterm placenta is less sensitive to pH changes compared to the enzyme from the term organ
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
similar level of expression of AMPD2, but greater expression of AMPD3 than in neurons
Manually annotated by BRENDA team
-
the study fails to confirm a survival benefit among heart failure patients carrying the AMPD1 T-allele (C34T)
Manually annotated by BRENDA team
-
activity of adenosine monophosphate deaminase is significantly higher in chicken of the fast-growing type than in the slow-growing French 'Label Rouge' type, and in heavy line typ
Manually annotated by BRENDA team
-
lower level of expression of both AMPD2 and AMPD3 than neurons, and a lower expression of AMPD3 than astrocytes
Manually annotated by BRENDA team
-
significantly increased FAC1 expression in the zygote, early embryo and endosperm. During somatic embryogenesis, a high level of FAC1 expression is observed in developing embryos including putative embryogenic cells. FAC1 represents one of the earliest expressed genes known in plants. It may act through AMP depletion to provide sufficient energy for the zygote to proceed through development
Manually annotated by BRENDA team
-
AMP-deaminase plays a role in formation of NH3 by endometrium stroma cells and its release into extracellular space during acetylcholine stimulation
Manually annotated by BRENDA team
-
significantly increased FAC1 expression in the zygote, early embryo and endosperm
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
from forebrain. In neurons AMPD2 exhibits 8fold greater expression than AMPD3
Manually annotated by BRENDA team
-
a macrophage-like cell line sensitive to anthrax lethal toxin, i.e. LeTx, induced death
Manually annotated by BRENDA team
-
smooth muscle
Manually annotated by BRENDA team
-
significantly increased FAC1 expression in the zygote, early embryo and endosperm
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
reversible association between the catalytic domain of the enzyme and the intracellular membrane
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
60000
-
the SDS-PAGE shows that the enzyme is not electrophoretically homogenous, with two bands present at a molecular mass between about 55000 and 60000 Da
85000
-
SDS-PAGE
92000
-
SDS-PAGE, 92 and 68 kDa fragments of the enzyme react with specificpolyclonal anti-(human) AMPD2 antibodies
140000 - 400000
-
3 different oligomeric enzyme forms of 140 kDa, 280 kDa, and 400 kDa, gel filtration
145000
-
gel filtration
150000
-
gel filtration
160000
-
myosin-bound enzyme, SDS-PAGE
276000
-
sucrose density gradient centrifugation
285000
-
sucrose density gradient centrifugation
320000
-
calculation from sedimentation constant and diffusion coefficient
330000
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oligomer
-
x * 68000, at least 3 different oligomeric forms of the enzyme, probably dimers, tetramers, and hexamers, SDS-PAGE
tetramer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
-
enzyme contains a histidine-proline-rich-glycoprotein HPRG component
phosphoprotein
-
the reversible phosphorylation adjusts enzyme function for an optimal role in controlling cellular adenylate levels in ischemic frozen muscle
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
3.3 A globular catalytic domain X-ray crystal structure with a bound herbicide-based transition state inhibitor (coformycin 5'-phosphate)
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 7.5
-
slowly reduces its activity on the both sides of the optimum pH 6.3, at pH values of 5.5, 7.0 and 7.5, AMPD shows 13, 31 and 65% lower activity, respectively
686221
6.8
-
highest stability
209672
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0 - 4
-
at high concentrations, 10 days
50
-
heating at 50C quickly destroys AMPD activity when the enzyme is incubated in distilled water, AMPD remains fully active over 30 min in the presence 1 M KCl at 50C
additional information
-
-
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
an apparent 10000 Da reduction in molecular mass of the native 85000 Da enzyme subunit with its conversion to a 75000 Da core is observed on storage of AMPD
-
ATP, ADP, GTP and alkali metal ions protect against heat inactivation
-
EDTA stabilizes the purified enzyme during storage
-
enzyme is associated to the histidine-proline-rich-glycoprotein HPRG via its catalytic subunit in a protein-protein complex, which is critical for the enzyme stability
-
freezing, unstable
-
heating in the presence of low KCl (150 mM) results in a rapid loss in activity with only 25% of initial activity being left after 30 min, about half of the initial activity remains after heating for 30 min in 25 mM histidine solution, solution, incubation in imidazole or phosphate solutions results in greater stability over 30 min of heating with AMPD activity decreasing by about 20%
-
phosphate stabilizes the tetrameric structure of the enzyme
-
repeated freezing and thawing, stable
-
sulfhydryl reagents and monovalent cations in high concentrations stabilize
-
additional information
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, 4 months, less than 10% loss of activity
-
0-4C or -20C for up to 10 days, 30 mg/ml protein
-
2-4C, 1 M KCl, at least 1 month, no loss of activity
-
2-4C, following the purification process when stored in 1 M KCl, 1 month, the enzyme is highly stable showing virtually no change in activity
-
4C, purified enzyme, loss of 50% activity within 1 week in absence of EDTA, in presence of EDTA it is stable for 10 days, fragmentation occurs at 4C
-
4C, several days, small loss of activity
-
storage of the muscle material as well as the purified enzyme increases the enzyme activity due to limited proteolytic cleavage
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
both native enzyme and its histidine-proline-rich-glycoprotein HPRG component, the latter being completely separated from the enzyme and its catalytic subunit by Zn2+-affinity chromatography including presence of 1 M KCl
-
expression in Escherichia coli
-
expression of AMPD1 and AMPD3 in Sf9 cells
-
native enzyme from human term and preterm placenta
-
partially
-
phosphocellulose column chromatography
Sephadex G50 gel filtration
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
AMPD3 expressed in Sf9 cells
-
expression in Escherichia coli
-
expression in Sf9 cells
-
expression of AMPD1 and AMPD3 in Sf9 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
AMP deaminase in the liver is elevated by 4.2fold in models of hepatotoxic injury as compared with controls. In acute hyperammonemia, activity of AMP deaminase increases by 59% in the neocortex. In the hippocampus of hyperammonemic rats, AMP deaminase activity is increased by 48%. Subacute hepatitis leads to 228% increase in AMP deaminase activity
-
during pregnancy the activity of AMP-deaminase in developing human placenta gradually decreases, being in homogenates of mature, term placenta (about 40 weeks of gestation) one fourth to one third of that in homogenates of immature (about 25 weeks of gestation) organ
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
DELTAL96
-
AMPD1 mutant, higher specific activity
DELTAM90
-
AMPD3 mutant, lower specific activity
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
-
assessment of synthetic nitro- and polycyclic musks, imidazolium ionic liquids and N-glucopyranosyl ammonium salts
medicine
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