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Information on EC 3.4.11.7 - glutamyl aminopeptidase and Organism(s) Mus musculus and UniProt Accession P16406
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3.4.11.7 glutamyl aminopeptidaseSpecify your search results
Word Map
- 3.4.11.7
- apa
- aminopeptidases
-
renin-angiotensin
- renin
-
dipeptidyl
-
hypertensive
- ras
- amastatin
-
brush
-
angiotensin-converting
-
antihypertensive
-
alanyl
- bestatin
- vasopressin
-
pressor
-
dipeptidylpeptidase
- losartan
-
exopeptidase
- enpep
-
arylamide
-
intracerebroventricularly
- angiotensinogen
- medicine
- sucrase-isomaltase
-
pyroglutamyl
-
3.2.1.20
-
puromycin-sensitive
-
ras-regulating
-
insulin-regulated
- oxytocinase
-
kininase
- beta-naphthylamide
- microvillar
- synthesis
- diagnostics
- drug development
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
release of N-terminal glutamate (and to a lesser extent aspartate) from a peptide
Synonyms
aminopeptidase a, angiotensinase, lap-a, gluap, glutamyl aminopeptidase, angiotensinase a, aspartyl-aminopeptidase, aminopeptidase-a, glutamyl-aminopeptidase, aspartate aminopeptidase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
aminopeptidase A
aminopeptidase, aspartate
-
-
-
-
angiotensinase A
-
-
-
-
APA
aspartate aminopeptidase
-
-
-
-
BP-1/6C3 antigen
-
-
-
-
Ca2+-activated glutamate aminopeptidase
-
-
-
-
Differentiation antigen gp160
-
-
-
-
EAP
-
-
-
-
glutamyl aminopeptidase
glutamyl peptidase
-
-
-
-
L-alpha-aspartyl(L-alpha-glutamyl)-peptide hydrolase
-
-
-
-
L-aspartate aminopeptidase
-
-
-
-
membrane aminopeptidase II
-
-
-
-
additional information
-
the enzyme belongs to the zinc-metallopeptidase family of zincins
aminopeptidase A
-
-
-
-
APA
-
-
-
-
glutamyl aminopeptidase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
release of N-terminal glutamate (and to a lesser extent aspartate) from a peptide
active site structure and organization, modeling, residues Glu352, Glu386, Tyr471, and Glu408 are important in catalysis
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PATHWAY SOURCE
PATHWAYS
-
-, -, -
CAS REGISTRY NUMBER
COMMENTARY
9074-83-3
-
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
alpha-L-aspartate-beta-naphthylamide + H2O
L-aspartate + beta-naphthylamine
high activity
-
-
?
alpha-L-glutamyl-beta-naphthylamide + H2O
L-glutamine + beta-naphthylamine
best substrate
-
-
?
L-alanine-beta-naphthylamide + H2O
L-alanine + beta-naphthylamine
low activity
-
-
?
L-lysine-beta-naphthylamide + H2O
L-lysine + beta-naphthylamine
low activity
-
-
?
N-(alpha-L-glutamyl)-4-nitroanilide + H2O
L-glutamic acid + 4-nitroaniline
-
-
-
?
N-(alpha-L-glutamyl)-beta-naphthylamide + H2O
L-glutamic acid + beta-naphthylamine
-
-
-
?
angiotensin II + H2O
aspartic acid + angiotensin III
-
angiotensin II: Asp-Arg-Val-Tyr-Ile-His-Pro-Phe
angiotensin III: Arg-Val-Tyr-Ile-His-Pro-Phe
-
?
angiotensin III + H2O
angiotensin IV + Arg
-
the enzyme is involved in regulation of blood pressure in the renin-angiotensin system in the brain causing hypertension
-
-
ir
Glu-2-naphthylamide + H2O
Glu + 2-naphthylamine
-
synthetic substrate used in the activity assay
-
-
?
N-(alpha-L-aspartylyl)-2-naphthylamide + H2O
L-aspartic acid + 2-naphthylamine
-
-
-
-
?
N-(alpha-L-glutamyl)-2-naphthylamide + H2O
L-glutamic acid + 2-naphthylamine
-
-
-
-
?
N-(alpha-L-glutamyl)-4-nitroanilide + H2O
L-glutamic acid + 4-nitroaniline
-
-
-
-
?
alpha-L-Glu-beta-naphthylamide + H2O
L-Glu + 2-naphthylamine
-
-
-
?
angiotensin II + H2O
Asp + angiotensin III
-
i.e. Asp-Arg-Val-Tyr-Ile-His-Pro-Phe
i.e. Arg-Val-Tyr-Ile-His-Pro-Phe
-
ir
angiotensin II + H2O
Asp + angiotensin III
-
angiotensin is the most active compound of the renin-angiotensin-system, RAS, involved in renal development
-
-
?
angiotensin II + H2O
Asp + angiotensin III
-
i.e. Asp-Tyr-Arg-Val-Tyr-Ile-His-Pro-Phe
i.e. Tyr-Arg-Val-Tyr-Ile-His-Pro-Phe
-
?
angiotensin II + H2O
Asp + angiotensin III
-
the enzyme is responsible for the convertion of angiotensin II into angiotensin III in the brain
-
-
?
additional information
?
-
association between elevated BP-1 expression and cell growth. The enzyme is not involved in immune system development
-
-
?
additional information
?
-
the S1' subsite is hydrophobic whereas the S2' subsite recognizes preferentially negatively charged residues derived from aspartic acid
-
-
?
additional information
?
-
the enzyme is involved in angiotensin metabolism
-
-
?
additional information
?
-
the enzyme catalyzes the hydrolysis of N-(alpha-L-glutamyl)- moieties more efficiently than the hydrolysis of alpha-L-aspartyl derivatives
-
-
?
additional information
?
-
enzyme APA cleaves the N-terminal glutamyl or aspartyl residue from peptide substrates
-
-
?
additional information
?
-
-
enzyme APA cleaves the N-terminal glutamyl or aspartyl residue from peptide substrates
-
-
?
additional information
?
-
-
The C-terminal domain of aminopeptidase A is an intramolecular chaperone required for the correct folding, cell surface expression, and activity of the enzyme
-
-
?
additional information
?
-
-
the enzyme catalyses the hydrolysis of N-terminal glutamic or aspartic acid residues from regulatory peptides, the enzyme is involved in metabolism of angiotensin II and angiotensin III in the brain, overview
-
-
?
additional information
?
-
-
the enzyme is involved in conversion of angiotensin II to angiotensin III and thus in controlling of vasopressin release and blood pressure, overview
-
-
?
additional information
?
-
-
substrate specificity, overview, the enzyme catalyses the hydrolysis of N-terminal glutamic or aspartic acid residues from regulatory peptides
-
-
?
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
angiotensin II + H2O
aspartic acid + angiotensin III
-
angiotensin II: Asp-Arg-Val-Tyr-Ile-His-Pro-Phe
angiotensin III: Arg-Val-Tyr-Ile-His-Pro-Phe
-
?
angiotensin III + H2O
angiotensin IV + Arg
-
the enzyme is involved in regulation of blood pressure in the renin-angiotensin system in the brain causing hypertension
-
-
ir
angiotensin II + H2O
Asp + angiotensin III
-
angiotensin is the most active compound of the renin-angiotensin-system, RAS, involved in renal development
-
-
?
angiotensin II + H2O
Asp + angiotensin III
-
the enzyme is responsible for the convertion of angiotensin II into angiotensin III in the brain
-
-
?
additional information
?
-
association between elevated BP-1 expression and cell growth. The enzyme is not involved in immune system development
-
-
?
additional information
?
-
the enzyme is involved in angiotensin metabolism
-
-
?
additional information
?
-
-
The C-terminal domain of aminopeptidase A is an intramolecular chaperone required for the correct folding, cell surface expression, and activity of the enzyme
-
-
?
additional information
?
-
-
the enzyme catalyses the hydrolysis of N-terminal glutamic or aspartic acid residues from regulatory peptides, the enzyme is involved in metabolism of angiotensin II and angiotensin III in the brain, overview
-
-
?
additional information
?
-
-
the enzyme is involved in conversion of angiotensin II to angiotensin III and thus in controlling of vasopressin release and blood pressure, overview
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Zinc
zinc-dependent metalloprotease, activity requires the HEXXH zinc-binding motif
Zn2+
Ca2+
Zn2+
Ca2+
7.3fold increase of ratio of turnover number to Km-value for the wild-type enzyme. Activity of mutant enzyme H450F is not measurable in absence of Ca2+. His450 together with Ca2+ may contribute to substrate specificity
Ca2+
each APA monomer contains one Ca2+ atom, Ca2+ (from 0 to 4 mM) increases the activity of the wild type enzyme
Ca2+
the presence of 4 mM Ca2+ enhances the enzymatic activity of wild type enzyme by a factor of 8
Ca2+
localized at the bottom of the S1 subsite, activates the enzyme and plays a key role of Arg878 together with Ca2 + in APA substrate specificity for N-terminal acidic amino acid residues by ensuring the optimal positioning of acidic substrates during catalysis. The Ca2+ atom interacts with the acidic side chains of Asp213 and Asp218, the carbonyl group of Glu215 and three water molecules, one of them being engaged in a hydrogen bond with the negatively charged carboxylate side chains of the inhibitors. Ca2+ activation profile of purified recombinant wild-type and mutated His-mAPAs, using an acidic substrate alpha-L-glutamyl-beta-naphthylamide, overview. Enzyme residue Arg878 does not contribute to Ca2+ binding in the S1 subsite
Zn2+
a zinc metalloprotease, Zn2+ atom is coordinated by the two histidine residues, His385 and His389, of the HEXXH motif, a water molecule, Glu408 of the WLNEG motif and either by one of the oxygen atoms of the phosphate of GluPO3H2, three-dimensional structure modelling
Zn2+
-
zinc-metallopeptidase, the enzyme contains the zinc-binding motif HEXXH residues 385-389 with catalytically important Glu386
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(S)-3-amino-4-mercapto-butyl sulfonic acid
i.e. EC33, a selective APA inhibitor, docking analysis in the presence of Ca2+, the ligand interacts with S1 subsite of Arg-878 in murine APA, three-dimensional structure modelling reavealing a change in the volume of the S1 subsite, which may impair the binding and/or the optimal positioning of the substrate in the active site as well as its hydrolysis, overview
4-amino-4-phosphonobutyric acid
a specific and selective APA inhibitor, a linear competitive inhibitor
RB150
selective and specific prodrug of the enzyme inhibitor EC33, inhibits the enzyme given i.v. to rats
[[(2R,3R)-3-amino-2-sulfhydryl-5-sulfonate]pentanoyl]-Ile-3-sulfoalanine-OH
-
[[(2R,3R)-3-amino-2-sulfhydryl-5-sulfonate]pentanoyl]-Tyr-homosulfoalanine-OH
-
[[(2S,3R)-3-amino-2-sulfhydryl-5-sulfonate]pentanoyl]-Ile-3-sulfoalanine-OH
-
[[(2S,3R)-3-amino-2-sulfhydryl-5-sulfonate]pentanoyl]-Tyr-homosulfoalanine-OH
-
(S)-3-amino-4-mercapto-butylsulfonic acid
-
specific and selective APA inhibitor
(S)-3-amino-4-mercaptobutyl sulfonic acid
-
EC33, specific and selective APA inhibitor
RB150
-
selective and specific prodrug of the enzyme inhibitor EC33, inhibits the enzyme given i.v. to mice
glutamate phosphonate
0.001 mM, activity of wild-type enzyme is completely abolished
amastatin
-
inhibits the enzyme and blocks the metabolism of brain angiotensin II and III
bestatin
-
inhibits the enzyme and blocks the metabolism of brain angiotensin II and III
Ca2+
-
Ca2+ up- or down-regulates the enzyme activity depending on the substrate tested
additional information
ligand docking study and molecular dynamics simulations with wild-type and mutant enzymes, overview
-
additional information
-
ligand docking study and molecular dynamics simulations with wild-type and mutant enzymes, overview
-
additional information
no enzyme inhibition by leptin, but reduction of enzyme level in blood, although not in kidney
-
additional information
-
no enzyme inhibition by leptin, but reduction of enzyme level in blood, although not in kidney
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ca2+
-
Ca2+ up- or down-regulates the enzyme activity depending on the substrate tested
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2.272
alpha-L-Asp-2-naphthylamide
pH 7.4, 37°C, mutant enzyme wild-type enzyme N353Q
2.307
alpha-L-Asp-2-naphthylamide
pH 7.4, 37°C, mutant enzyme wild-type enzyme N353A
1.943
alpha-L-Glu-2-naphthylamide
pH 7.4, 37°C, mutant enzyme wild-type enzyme N353A
2.687
alpha-L-Glu-2-naphthylamide
pH 7.4, 37°C, mutant enzyme wild-type enzyme N353Q
0.171
alpha-L-Glu-beta-naphthylamide
pH 7.4, 37°C, wild-type enzyme, in presence of 4 mM Ca2+
0.432
alpha-L-Glu-beta-naphthylamide
pH 7.4, 37°C, wild-type enzyme, in presence of 0.025 mM Ca2+
0.697
alpha-L-Glu-beta-naphthylamide
pH 7.4, 37°C, wild-type enzyme, without Ca2+
4.383
alpha-L-Glu-beta-naphthylamide
pH 7.4, 37°C, mutant enzyme H450F enzyme, in presence of 4 mM Ca2+
5.94
alpha-L-Glu-beta-naphthylamide
pH 7.4, 37°C, mutant enzyme H450F, in presence of 0.025 mM Ca2+
0.0391
alpha-L-glutamyl-beta-naphthylamide
pH 7.4, temperature not specified in the publication, recombinant His-tagged wild-type enzyme, with 4 mM Ca2+
0.165
alpha-L-glutamyl-beta-naphthylamide
pH 7.4, temperature not specified in the publication, recombinant His-tagged wild-type enzyme
0.221
alpha-L-glutamyl-beta-naphthylamide
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878A, with 4 mM Ca2+
0.269
alpha-L-glutamyl-beta-naphthylamide
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878K, with 4 mM Ca2+
1.5
alpha-L-glutamyl-beta-naphthylamide
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878A
12.5
alpha-L-glutamyl-beta-naphthylamide
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878K
0.159
L-Glu-2-naphthylamide
recombinant mutant enzyme T348S, in 50 mM Tris-HCl buffer, pH 7.4, in the presence of 4 mM Ca2+
0.198
L-Glu-2-naphthylamide
recombinant wild type enzyme, in 50 mM Tris-HCl buffer, pH 7.4, in the presence of 4 mM Ca2+
0.258
L-Glu-2-naphthylamide
recombinant mutant enzyme T348D, in 50 mM Tris-HCl buffer, pH 7.4, in the presence of 4 mM Ca2+
0.282
L-Glu-2-naphthylamide
recombinant mutant enzyme T348Y, in 50 mM Tris-HCl buffer, pH 7.4, in the presence of 4 mM Ca2+
1.136
L-Glu-2-naphthylamide
recombinant mutant enzyme T348D, in 50 mM Tris-HCl buffer, pH 7.4, in the absence of Ca2+
1.481
L-Glu-2-naphthylamide
recombinant wild type enzyme, in 50 mM Tris-HCl buffer, pH 7.4, in the absence of Ca2+
1.919
L-Glu-2-naphthylamide
recombinant mutant enzyme T348Y, in 50 mM Tris-HCl buffer, pH 7.4, in the absence of Ca2+
2.034
L-Glu-2-naphthylamide
recombinant mutant enzyme T348S, in 50 mM Tris-HCl buffer, pH 7.4, in the absence of Ca2+
0.152
L-Glu-p-nitroanilide
wild type enzyme, in absence of Ca2+, in 50 mM Tris/HCl buffer (pH 7.4), at 37°C
1.475
L-Glu-p-nitroanilide
wild type enzyme, in absence of Ca2+, in 50 mM Tris/HCl buffer (pH 7.4), at 37°C
additional information
additional information
Michaelis-Menten kinetics
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
14
alpha-L-Asp-2-naphthylamide
pH 7.4, 37°C, mutant enzyme wild-type enzyme N353A
25
alpha-L-Asp-2-naphthylamide
pH 7.4, 37°C, mutant enzyme wild-type enzyme N353Q
184
alpha-L-Glu-2-naphthylamide
pH 7.4, 37°C, mutant enzyme wild-type enzyme N353Q
227
alpha-L-Glu-2-naphthylamide
pH 7.4, 37°C, mutant enzyme wild-type enzyme N353A
1.8
alpha-L-Glu-beta-naphthylamide
pH 7.4, 37°C, mutant enzyme H450F, in presence of 0.025 mM Ca2+
7.5
alpha-L-Glu-beta-naphthylamide
pH 7.4, 37°C, mutant enzyme H450F enzyme, in presence of 4 mM Ca2+
93
alpha-L-Glu-beta-naphthylamide
pH 7.4, 37°C, wild-type enzyme, without Ca2+
149
alpha-L-Glu-beta-naphthylamide
pH 7.4, 37°C, wild-type enzyme, in presence of 0.025 mM Ca2+
166
alpha-L-Glu-beta-naphthylamide
pH 7.4, 37°C, wild-type enzyme, in presence of 4 mM Ca2+
3.12
alpha-L-glutamyl-beta-naphthylamide
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878K
4.95
alpha-L-glutamyl-beta-naphthylamide
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878A
13.9
alpha-L-glutamyl-beta-naphthylamide
pH 7.4, temperature not specified in the publication, recombinant His-tagged wild-type enzyme
22.4
alpha-L-glutamyl-beta-naphthylamide
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878A, with 4 mM Ca2+
81.7
alpha-L-glutamyl-beta-naphthylamide
pH 7.4, temperature not specified in the publication, recombinant His-tagged wild-type enzyme, with 4 mM Ca2+
135
alpha-L-glutamyl-beta-naphthylamide
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878K, with 4 mM Ca2+
2 - 8
L-Glu-2-naphthylamide
recombinant mutant enzyme T348Y, in 50 mM Tris-HCl buffer, pH 7.4, in the absence of Ca2+
40
L-Glu-2-naphthylamide
recombinant mutant enzyme T348D, in 50 mM Tris-HCl buffer, pH 7.4, in the presence of 4 mM Ca2+
92
L-Glu-2-naphthylamide
recombinant mutant enzyme T348D, in 50 mM Tris-HCl buffer, pH 7.4, in the absence of Ca2+
167
L-Glu-2-naphthylamide
recombinant mutant enzyme T348Y, in 50 mM Tris-HCl buffer, pH 7.4, in the presence of 4 mM Ca2+
256
L-Glu-2-naphthylamide
recombinant wild type enzyme, in 50 mM Tris-HCl buffer, pH 7.4, in the presence of 4 mM Ca2+
292
L-Glu-2-naphthylamide
recombinant wild type enzyme, in 50 mM Tris-HCl buffer, pH 7.4, in the absence of Ca2+
575
L-Glu-2-naphthylamide
recombinant mutant enzyme T348S, in 50 mM Tris-HCl buffer, pH 7.4, in the presence of 4 mM Ca2+
640
L-Glu-2-naphthylamide
recombinant mutant enzyme T348S, in 50 mM Tris-HCl buffer, pH 7.4, in the absence of Ca2+
295
L-Glu-p-nitroanilide
wild type enzyme, in absence of Ca2+, in 50 mM Tris/HCl buffer (pH 7.4), at 37°C
720
L-Glu-p-nitroanilide
wild type enzyme, in absence of Ca2+, in 50 mM Tris/HCl buffer (pH 7.4), at 37°C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.3
alpha-L-glutamyl-beta-naphthylamide
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878K
3.3
alpha-L-glutamyl-beta-naphthylamide
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878A
84.3
alpha-L-glutamyl-beta-naphthylamide
pH 7.4, temperature not specified in the publication, recombinant His-tagged wild-type enzyme
102
alpha-L-glutamyl-beta-naphthylamide
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878A, with 4 mM Ca2+
502
alpha-L-glutamyl-beta-naphthylamide
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878K, with 4 mM Ca2+
2090
alpha-L-glutamyl-beta-naphthylamide
pH 7.4, temperature not specified in the publication, recombinant His-tagged wild-type enzyme, with 4 mM Ca2+
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00007
N-(2-aminoethyl)-4-methyl-5-sulfanyl-pentanamide
wild type enzyme, in 50 mM Tris/HCl buffer (pH 7.4), 4 mM Ca2+, at 37°C
0.000292
[[(2R,3R)-3-amino-2-sulfhydryl-5-sulfonate]pentanoyl]-D-Ile-Asp-OH
pH 7.3, 37°C
0.0000833
[[(2R,3R)-3-amino-2-sulfhydryl-5-sulfonate]pentanoyl]-Ile-3-sulfoalanine-OH
pH 7.3, 37°C
0.000283
[[(2R,3R)-3-amino-2-sulfhydryl-5-sulfonate]pentanoyl]-Ile-D-Asp-OH
pH 7.3, 37°C
0.0042
[[(2R,3R)-3-amino-2-sulfhydryl-5-sulfonate]pentanoyl]-Ile-NH2
pH 7.3, 37°C
0.0012
[[(2R,3R)-3-amino-2-sulfhydryl-5-sulfonate]pentanoyl]-Ile-OH
pH 7.3, 37°C
0.000027
[[(2R,3R)-3-amino-2-sulfhydryl-5-sulfonate]pentanoyl]-Tyr-Asp-OH
pH 7.3, 37°C
0.0000733
[[(2R,3R)-3-amino-2-sulfhydryl-5-sulfonate]pentanoyl]-Tyr-homosulfoalanine-OH
pH 7.3, 37°C
0.000267
[[(2R,3R)-3-amino-5-carboxylate-2-sulfhydryl]pentanoyl]-Ile-Asp-OH
pH 7.3, 37°C
0.00091
[[(2R,3R)-3-amino-5-phosphonate-2-sulfhydryl]pentanoyl]-Ile-Asp-OH
pH 7.3, 37°C
0.00005
[[(2R,3S)-3-amino-2-sulfhydryl-5-sulfonate]pentanoyl]-Ile-Asp-OH
pH 7.3, 37°C
0.000016
[[(2R,3S)-3-amino-5-carboxylate-2-sulfhydryl]pentanoyl]-Ile-Asp-OH
pH 7.3, 37°C
0.000051
[[(2RS,3RS)-3-amino2-sulfhydryl-5-sulfamoyl]pentane]-Ile-Asp-OH
pH 7.3, 37°C
0.00008
[[(2RS,3RS)-3-amino2-sulfhydryl-5-sulfamoyl]pentanoyl]-Ile-Asp-OH
pH 7.3, 37°C
0.00015
[[(2RS,3RS)-3-amino2-sulfhydryl-5-sulfamoyl]pentanoyl]-Tyr-Asp-OH
pH 7.3, 37°C
0.0000147
[[(2S,3R)-3-amino-2-sulfhydryl-5-sulfonate]pentanoyl]-D-Ile-Asp-OH
pH 7.3, 37°C
0.0000036
[[(2S,3R)-3-amino-2-sulfhydryl-5-sulfonate]pentanoyl]-Ile-3-sulfoalanine-OH
pH 7.3, 37°C
0.00000536
[[(2S,3R)-3-amino-2-sulfhydryl-5-sulfonate]pentanoyl]-Ile-D-Asp-OH
pH 7.3, 37°C
0.000145
[[(2S,3R)-3-amino-2-sulfhydryl-5-sulfonate]pentanoyl]-Ile-NH2
pH 7.3, 37°C
0.00004
[[(2S,3R)-3-amino-2-sulfhydryl-5-sulfonate]pentanoyl]-Ile-OH
pH 7.3, 37°C
0.0000043
[[(2S,3R)-3-amino-2-sulfhydryl-5-sulfonate]pentanoyl]-Tyr-Asp-OH
pH 7.3, 37°C
0.0000093
[[(2S,3R)-3-amino-2-sulfhydryl-5-sulfonate]pentanoyl]-Tyr-homosulfoalanine-OH
pH 7.3, 37°C
0.00000356
[[(2S,3R)-3-amino-5-carboxylate-2-sulfhydryl]pentanoyl]-Ile-Asp-OH
pH 7.3, 37°C
0.000012
[[(2S,3R)-3-amino-5-phosphonate-2-sulfhydryl]pentanoyl]-Ile-Asp-OH
pH 7.3, 37°C
0.00002
[[(2S,3S)-3-amino-2-sulfhydryl-5-sulfonate]pentanoyl]-Ile-Asp-OH
pH 7.3, 37°C
0.000013
[[(2S,3S)-3-amino-5-carboxylate-2-sulfhydryl]pentanoyl]-Ile-Asp-OH
pH 7.3, 37°C
0.000314
(4R)-4-amino-5-sulfanylpentanoic acid
pH 7.4, temperature not specified in the publication, recombinant His-tagged wild-type enzyme, with 4 mM Ca2+
0.00157
(4R)-4-amino-5-sulfanylpentanoic acid
pH 7.4, temperature not specified in the publication, recombinant His-tagged wild-type enzyme
0.00172
(4R)-4-amino-5-sulfanylpentanoic acid
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878A
0.01
(4R)-4-amino-5-sulfanylpentanoic acid
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878K
0.000268
(S)-3-amino-4-mercapto-butyl sulfonic acid
pH 7.4, temperature not specified in the publication, recombinant His-tagged wild-type enzyme, with 4 mM Ca2+
0.00152
(S)-3-amino-4-mercapto-butyl sulfonic acid
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878K, with 4 mM Ca2+
0.002
(S)-3-amino-4-mercapto-butyl sulfonic acid
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878A, with 4 mM Ca2+
0.000118
2,6-diaminohexane-1-thiol
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878A
0.000317
2,6-diaminohexane-1-thiol
pH 7.4, temperature not specified in the publication, recombinant His-tagged wild-type enzyme
0.000378
2,6-diaminohexane-1-thiol
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878K
0.00751
2,6-diaminohexane-1-thiol
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878A, with 4 mM Ca2+
0.0134
2,6-diaminohexane-1-thiol
pH 7.4, temperature not specified in the publication, recombinant His-tagged wild-type enzyme, with 4 mM Ca2+
0.0139
2,6-diaminohexane-1-thiol
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878K, with 4 mM Ca2+
0.000074
4-amino-4-phosphonobutyric acid
pH 7.4, temperature not specified in the publication, recombinant His-tagged wild-type enzyme, with 4 mM Ca2+
0.000619
4-amino-4-phosphonobutyric acid
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878K, with 4 mM Ca2+
0.0065
4-amino-4-phosphonobutyric acid
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878A, with 4 mM Ca2+
0.000038
glutamate phosphonic acid
pH 7.4, 37°C, wild-type enzyme, 4 mM Ca2+
0.00061
glutamate phosphonic acid
pH 7.4, 37°C, wild-type enzyme, 0.025 mM Ca2+
0.00084
glutamate phosphonic acid
pH 7.4, 37°C, mutant enzyme H450F, 4 mM Ca2+
0.00287
glutamate phosphonic acid
pH 7.4, 37°C, wild-type enzyme, no Ca2+
0.056
glutamate phosphonic acid
pH 7.4, 37°C, mutant enzyme H450F, 0.025 mM Ca2+
0.00038
glutamate thiol
mutant enzyme T348S, in 50 mM Tris-HCl buffer, pH 7.4, in the presence of 4 mM Ca2+
0.00085
glutamate thiol
mutant enzyme T348Y, in 50 mM Tris-HCl buffer, pH 7.4, in the presence of 4 mM Ca2+
0.00103
glutamate thiol
mutant enzyme T348D, in 50 mM Tris-HCl buffer, pH 7.4, in the presence of 4 mM Ca2+
0.0011
glutamate thiol
wild type enzyme, in 50 mM Tris-HCl buffer, pH 7.4, in the absence of Ca2+
0.00194
glutamate thiol
mutant enzyme T348S, in 50 mM Tris-HCl buffer, pH 7.4, in the absence of Ca2+
0.00197
glutamate thiol
mutant enzyme T348D, in 50 mM Tris-HCl buffer, pH 7.4, in the absence of Ca2+
0.002
glutamate thiol
wild type enzyme, in 50 mM Tris-HCl buffer, pH 7.4, in the presence of 4 mM Ca2+
0.00206
glutamate thiol
mutant enzyme T348Y, in 50 mM Tris-HCl buffer, pH 7.4, in the absence of Ca2+
0.0001
lysine thiol
mutant enzyme T348S, in 50 mM Tris-HCl buffer, pH 7.4, in the absence of Ca2+
0.00022
lysine thiol
wild type enzyme, in 50 mM Tris-HCl buffer, pH 7.4, in the absence of Ca2+
0.00026
lysine thiol
mutant enzyme T348Y, in 50 mM Tris-HCl buffer, pH 7.4, in the absence of Ca2+
0.0009
lysine thiol
mutant enzyme T348D, in 50 mM Tris-HCl buffer, pH 7.4, in the absence of Ca2+
0.00275
lysine thiol
mutant enzyme T348S, in 50 mM Tris-HCl buffer, pH 7.4, in the presence of 4 mM Ca2+
0.00298
lysine thiol
wild type enzyme, in 50 mM Tris-HCl buffer, pH 7.4, in the presence of 4 mM Ca2+
0.0036
lysine thiol
mutant enzyme T348Y, in 50 mM Tris-HCl buffer, pH 7.4, in the presence of 4 mM Ca2+
0.00394
lysine thiol
mutant enzyme T348D, in 50 mM Tris-HCl buffer, pH 7.4, in the presence of 4 mM Ca2+
0.00019
methionine thiol
mutant enzyme T348S, in 50 mM Tris-HCl buffer, pH 7.4, in the absence of Ca2+
0.00026
methionine thiol
mutant enzyme T348D, in 50 mM Tris-HCl buffer, pH 7.4, in the absence of Ca2+
0.00029
methionine thiol
mutant enzyme T348Y, in 50 mM Tris-HCl buffer, pH 7.4, in the absence of Ca2+
0.00058
methionine thiol
wild type enzyme, in 50 mM Tris-HCl buffer, pH 7.4, in the absence of Ca2+
0.00307
methionine thiol
mutant enzyme T348Y, in 50 mM Tris-HCl buffer, pH 7.4, in the presence of 4 mM Ca2+
0.00403
methionine thiol
mutant enzyme T348S, in 50 mM Tris-HCl buffer, pH 7.4, in the presence of 4 mM Ca2+
0.00667
methionine thiol
mutant enzyme T348D, in 50 mM Tris-HCl buffer, pH 7.4, in the presence of 4 mM Ca2+
0.0084
methionine thiol
wild type enzyme, in 50 mM Tris-HCl buffer, pH 7.4, in the presence of 4 mM Ca2+
0.000475
methionine-thiol
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878A
0.00075
methionine-thiol
pH 7.4, temperature not specified in the publication, recombinant His-tagged wild-type enzyme
0.00125
methionine-thiol
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878K
0.00322
methionine-thiol
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878A
0.00514
methionine-thiol
pH 7.4, temperature not specified in the publication, recombinant His-tagged mutant R878K
0.00918
methionine-thiol
pH 7.4, temperature not specified in the publication, recombinant His-tagged wild-type enzyme, with 4 mM Ca2+
0.000053
[[(2R,3R)-3-amino-2-sulfhydryl-5-sulfonate]pentanoyl]-Ile-Asp-OH
pH 7.3, 37°C
0.00047
[[(2R,3R)-3-amino-2-sulfhydryl-5-sulfonate]pentanoyl]-Ile-Asp-OH
pH 7.3, 37°C
0.0000032
[[(2S,3R)-3-amino-2-sulfhydryl-5-sulfonate]pentanoyl]-Ile-Asp-OH
pH 7.3, 37°C
0.000015
[[(2S,3R)-3-amino-2-sulfhydryl-5-sulfonate]pentanoyl]-Ile-Asp-OH
pH 7.3, 37°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.06
0.09
-
aminopeptidase A activity, tegmentum/colliculi, aminopeptidase A-deficient mice
11
-
aminopeptidase A activity depending on alcohol, lung, wild-type mice, without access to a 10% ethanol solution
21
-
aminopeptidase A activity depending on alcohol, kidney, wild-type mice, without access to a 10% ethanol solution
26
-
aminopeptidase A activity depending on alcohol, kidney, wild-type mice, with access to a 10% ethanol solution
7
-
aminopeptidase A activity depending on alcohol, lung, wild-type mice, with access to a 10% ethanol solution
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
7.4
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
activity is restricted to progenitor and precursor B cells. Enhanced BP-1 expression on virus-transformed pre-B cells and on normal pro-B cells stimulated by the interleukin 7 growth factor
additional information
-
the enzyme's ectodomain is cleaved in the kidney in to an N-terminal fragment, corresponding to the zinc metallopeptidase domain, and a C-terminal fragment
additional information
quantitative real-time PCR enzyme expression analysis
additional information
-
the enzyme is absent in the medulla and renal arterioles, distribution in renal tissues, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
deletion of the C-terminal domain abolishes the maturation and enzymatic activity of the N-terminal domain, which remains in the endoplasmic reticulum bound to calnexin as unfolded protein
-
of CHO cells, wild-type and mutant enzymes N353Q and N353A exhibit membrane expression
wild-type and mutant enzymes in stably transfected mutant enzymes
-
bound, type II integral membrane protein, the enzyme contains an ectodomain
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
additional information
malfunction
higher APA activity is observed in the kidney and lower activity in lung of ob/ob mice. High aminopeptidase A (APA) activity contributes to blood pressure control in ob/ob mice through an AT2 receptor-dependent mechanism
malfunction
mutagenic replacement of Arg-878 with an alanine or a lysine residue decreases the affinity of the recombinant enzymes for the acidic substrate, alpha-L-glutamyl-beta-naphthylamide, with a slight decrease in substrate hydrolysis velocity either with or without Ca2+. In the absence of Ca2+, the mutations modify the substrate specificity of enzyme APA for the acidic substrate. The mutated enzymes hydrolyse more efficiently basic and neutral substrates, although the addition of Ca2+ partially restores the acidic substrate specificity
physiological function
aminopeptidase A (APA) is a membrane-bound zinc metalloprotease cleaving, in the brain, the N-terminal aspartyl residue of angiotensin II to generate angiotensin III, which exerts a tonic stimulatory effect on the control of blood pressure in hypertensive animals
physiological function
aminopeptidase A enzyme metabolizes angiotensin (ANG) II into ANG III, a peptide associated with intrarenal angiotensin type 2 (AT2) receptor activation and induction of natriuresis. Role of AT2 receptor and APA as active mechanisms regulating blood pressure in ob/ob mice, overview
additional information
residue Arg878 together with Ca2+ is responsible in mouse aminopeptidase A for the substrate specificity for N-terminal acidic amino-acid residues by ensuring the optimal positioning of acidic substrates during catalysis. Docking and molecular dynamics simulations using the crystal structure of human aminopeptidase A complexed with Glu and Ca2+, PDB ID 4KXD, overview
additional information
-
residue Arg878 together with Ca2+ is responsible in mouse aminopeptidase A for the substrate specificity for N-terminal acidic amino-acid residues by ensuring the optimal positioning of acidic substrates during catalysis. Docking and molecular dynamics simulations using the crystal structure of human aminopeptidase A complexed with Glu and Ca2+, PDB ID 4KXD, overview
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). AMPE_MOUSE
945
1
107956
Swiss-Prot
other Location (Reliability: 4)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
140000
147000
160000
107000
-
only the catalytic part of the extracellular domain of the membrane-spanning protein
45000
-
only the C-terminal domain of the extracellular domain, obtained by proteolytic fragmentation
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
additional information
dimer
-
full-length enzyme forms a dimer via a disulfide bond, this bond is not essential for dimer formation or enzymatic activity
additional information
aminopeptidase A (APA) is a 160 kDa homodimeric type II Zn2+ membrane-bound aminopeptidase
additional information
-
aminopeptidase A (APA) is a 160 kDa homodimeric type II Zn2+ membrane-bound aminopeptidase
additional information
-
the C-terminal domain is required for enzyme maturation, N-terminal domain activation, and cell surface localization, deletion of the C-terminal domain abolishes the maturation and enzymatic activity of the N-terminal domain, which remains in the endoplasmic reticulum bound to calnexin as unfolded protein
additional information
-
three-dimensional structure determination and analysis, modeling, the enzyme contains a short N-terminal cytoplasmic domain of 17 amino acid residues, a transmembrane domain of 22 amino acid residues, and a large extracellular domain of 906 amino acid residues in cluding the active and the zinc-binding site
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
glycoprotein
proteolytic modification
-
the enzyme's ectodomain is cleaved in the kidney in to an N-terminal fragment, corresponding to the zinc metallopeptidase domain, and a C-terminal fragment
glycoprotein
wild-type enzyme and the mutant enzymes N353Q and N353A are equally glycosylated, mutant enzyme N353S is partially glycosylated
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C43S
mutant enzyme is monomeric under reducing and under non-reducing conditions, specific activity of the mutant enzyme is similar to that of the wild-type enzyme
D227A
mutant enzyme produces only the 140000 Da enzyme form by SDS-PAGE and autoradiography compared to a 168000 Da enzyme form and a 140000 Da enzyme form of the wild-type enzyme. Mutant enzyme displays incorrect maturation and trafficking. Mutant enzyme shows 0.18% of the wild-type activity
D227R
mutant enzyme produces only the 140000 Da enzyme form by SDS-PAGE and autoradiography compared to a 168000 Da enzyme form and a 140000 Da enzyme form of the wild-type enzyme. Mutant enzyme displays incorrect maturation and trafficking
E215A
the ratio of turnover number to KM-value for the substrate alpha-L-Glu-beta-naphthylamide is 10% of that of the wild-type enzyme. 68fold increase in KI-value for glutamate-thiol, 466fold increase in KI-value for L-glutamate phosphonic acid, 5.8fold increase in Ki-value for D-glutamate phosphonic acid
E215D
the ratio of turnover number to KM-value for the substrate alpha-L-Glu-beta-naphthylamide is 7% of that of the wild-type enzyme. 49fold increase in KI-value for glutamate-thiol, 266fold increase in KI-value for L-glutamate phosphonic acid, 2.6fold increase in Ki-value for D-glutamate phosphonic acid
E215Q
1.2fold increase in the ratio of turnover number to KM-value for the substrate alpha-L-Glu-beta-naphthylamide. 2.3fold increase in KI-value for glutamate-thiol, 5.8fold increase in KI-value for L-glutamate phosphonic acid, 8.4fold increase in Ki-value for D-glutamate phosphonic acid
H450F
mutation markedly lowers the level of enzyme activity and changes the sensitivity to Ca2+, The EC50 for Ca2+ is 0.025 mM in the wild-type enzyme and 0.279 mM in the mutant enzyme. 15.5fold increase of KI-value for glutamate-thiol in presence of 0.025 mM Ca2+, 18.9fold increase of KI-value for glutamate-thiol in presence of 4 mM Ca2+, 91.8fold increase of Ki-value for glutamate phosphonic acid in presence of 0.025 mM Ca2+, 22.1fold increase of Ki-value for glutamate phosphonic acid in presence of 4 mM Ca2+, 2.5fold increase of Ki-value for lysine-thiol in presence of 0.025 mM Ca2+, 2.76fold increase of Ki-value for lysine-thiol in presence of 4 mM Ca2+. Mutant enzyme shows a 1150fold decrease in the ratio of turnover number to Km-value for alpha-L-Glu-beta-naphthylamide in presence of 0.025 mM Ca2+. Mutant enzyme shows a 571fold decrease in the ratio of turnover number to Km-value for alpha-L-Glu-beta-naphthylamide in presence of 5 mM Ca2+
N353A
the ratio of turnover number to Km-value is 7% of the wild-type value with alpha-L-Glu-2-naphthylamide as substrate, the ratio of turnover number to Km-value is 3% of the wild-type value with angiotensin II as substrate. The Ki-value for glutamate-thiol is 9.3fold higher than the wild-type value, the Ki-value for glutamine-thiol is 4.3fold higher than the wild-type value, the Ki-value for L-glutamate phosphonic acid is 6.6fold higher than the wild-type value, the Ki-value for D-glutamate phosphonic acid is 3.4fold higher than the wild-type value, the Ki-value for captopril is 86% of the wild-type value. Mutant enzyme is similarly routed and glycosylated to the wild-type enzyme
N353D
mutant enzyme exhibits weak and unstable activity, mutant enzyme is trapped intracellularly and partially glycosylated
N353Q
the ratio of turnover number to Km-value is 4% of the wild-type value with alpha-L-Glu-2-naphthylamide as substrate, the ratio of turnover number to Km-value is 7% of the wild-type value with alpha-L-Asp-2-naphthylamide as substrate, the ratio of turnover number to Km-value is 5% of the wild-type value with angiotensin II as substrate.The Ki-value for glutamate-thiol is 6.3fold higher than the wild-type value, the Ki-value for glutamine-thiol is 4.4fold higher than the wild-type value, the Ki-value for L-glutamate phosphonic acid is 3.57fold higher than the wild-type value, the Ki-value for D-glutamate phosphonic acid is 1.5fold higher than the wild-type value, the Ki-value for captopril is 2fold higher than the wild-type value. Mutant enzyme is similarly routed and glycosylated to the wild-type enzyme
R220A
mutant enzyme produces only the 140000 Da enzyme form by SDS-PAGE and autoradiography compared to a 168000 Da enzyme form and a 140000 Da enzyme form of the wild-type enzyme. Mutant enzyme displays incorrect maturation and trafficking. Mutant enzyme shows 0.3% of the wild-type activity
R220D
mutant enzyme produces only the 140000 Da enzyme form by SDS-PAGE and autoradiography compared to a 168000 Da enzyme form and a 140000 Da enzyme form of the wild-type enzyme. Mutant enzyme displays incorrect maturation and trafficking
R220D/D227R
mutant enzyme produces only the 140000 Da enzyme form by SDS-PAGE and autoradiography compared to a 168000 Da enzyme form and a 140000 Da enzyme form of the wild-type enzyme. Mutant enzyme displays incorrect maturation and trafficking
R878A
site-directed mutagenesis, the mutant shows decreased affinity for the acidic substrate, alpha-L-glutamyl-beta-naphthylamide, with a slight decrease in substrate hydrolysis velocity either with or without Ca2+ compared to the wild-type enzyme. Analysis of the 3D models of the Arg878 mutated APAs reveals a change in the volume of the S1 subsite, which may impair the binding and/or the optimal positioning of the substrate in the active site as well as its hydrolysis
R878K
site-directed mutagenesis, the mutant shows decreased affinity for the acidic substrate, alpha-L-glutamyl-beta-naphthylamide, with a slight decrease in substrate hydrolysis velocity either with or without Ca2+ compared to the wild-type enzyme. Analysis of the 3D models of the Arg878 mutated APAs reveals a change in the volume of the S1 subsite, which may impair the binding and/or the optimal positioning of the substrate in the active site as well as its hydrolysis
T348D
the mutation leads to a modification of the hydrolysis velocity, with no change in the affinity of the recombinant enzymes for the substrate L-Glu-2-naphthylamide, either in the absence or presence of Ca2+
T348S
mutant with increased activity, the mutation leads to a modification of the hydrolysis velocity, with no change in the affinity of the recombinant enzymes for the substrate L-Glu-2-naphthylamide, either in the absence or presence of Ca2+
T348Y
mutant with strongly reduced activity, the mutation leads to a modification of the hydrolysis velocity, with no change in the affinity of the recombinant enzymes for the substrate L-Glu-2-naphthylamide, either in the absence or presence of Ca2+
additional information
additional information
substitution mutations at Asp218 and Asp213 maintain the ability of APA to be activated by Ca2+ and induce a decrease of the inhibitory potencies of inhibitors homologous with acidic residues
additional information
-
substitution mutations at Asp218 and Asp213 maintain the ability of APA to be activated by Ca2+ and induce a decrease of the inhibitory potencies of inhibitors homologous with acidic residues
additional information
Ca2+ activation profile of purified recombinant wild-type and mutated His-mAPAs, using an acidic substrate alpha-L-glutamyl-beta-naphthylamide, overview
additional information
-
Ca2+ activation profile of purified recombinant wild-type and mutated His-mAPAs, using an acidic substrate alpha-L-glutamyl-beta-naphthylamide, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme from COS-7 cells by BP-1 antibody affinity chromatography
recombinant His-tagged wild-type and mutant enzymes from CHO-K1 cells by Co2+ affinity chromatography
Talon Co2+ column chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
BP-1/6C3 antigen, gene ENPEP, full-length DNA and amino acid sequence determination and analysis, genetic structure, determination of 5'-flanking regions, promoter sequence, and DNA-binding motifs for transcription factors, overview, transient or stable expression of recombinant enzyme with transmembrane regions or cytoplasmic regions by human interleukin 4 leader sequence in COS-7 cells
recombinant expression of His-tagged wild-type and mutant enzymes in CHO-K1 cells
expression of His-tagged or FLAG-tagged wild-type enzyme, and of isolated His- or FLAG-tagged N-terminal, and HA-tagged C-terminal domain in CHO-K1 cells and AtT-20 cells, expression in trans of the separate C- and N-terminal domains rescues enzyme functions, overview
-
gene APA, DNA and amino acid sequence determination and analysis, genetic organization and structure
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
long-term leptin treatment reduces APA activity in the blood but not in kidney, but incubation of ob/+ and ob/ob mice with leptin does not change APA activity
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
development of potent and selective APA inhibitors crossing the blood-brain barrier after oral administration for use as centrally-acting antihypertensive agents
medicine
medicine
-
the enzyme might be a target in treatment of salt-dependent hypertension with RB150 as an antihypertensive agent
medicine
-
aminopeptidases play an important role in the regulation of blood pressure, and in the regulation of other pathophysiological processes such as angiogenesis, antigen-presentation, and fertility most probably by mediating the metabolism of some peptide substrates
medicine
-
central APA is a potential therapeutic target for the treatment of hypertension
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Zini, S.; Fournie-Zaluski, M.C.; Chauvel, E.; Roques, B.P.; Corvol, P.; Llorens-Cortes, C.
Identification of metabolic pathways of brain angiotensin II and III using specific aminopeptidase inhibitors: predominant role of angiotensin III in the control of vasopressin release
Proc. Natl. Acad. Sci. USA
93
11968-11973
1996
Mus musculus
Vazeux, G.; Wilk, S.; Wilk, E.; Corvol, P.; Llorens-Cortez, C.
Production and properties of a recombinant soluble form of aminopeptidase A
Eur. J. Biochem.
254
671-678
1998
Mus musculus
Llorens-Cortes, C.
Identification of metabolic pathways of brain angiotensin II and III using specific aminopeptidase inhibitors: Predominant role of angiotensin III in the control of vasopressin release
C. R. Seances Soc. Biol. Fil.
192
607-618
1998
Mus musculus
Wu, Q.; Lahti, J.M.; Air, G.M.; Burrows, P.D.; Cooper, M.D.
Molecular cloning of the murine BP-1/6C3 antigen: a member of the zinc-dependent metallopeptidase family
Proc. Natl. Acad. Sci. USA
87
993-997
1990
Mus musculus
Ofner, L.D.; Hooper, N.M.
The C-terminal domain, but not the interchain disulphide, is required for the activity and intracellular trafficking of aminopeptidase A
Biochem. J.
362
191-197
2002
Mus musculus (P16406), Mus musculus
Georgiadis, D.; Vazeux, G.; Llorens-Cortes, C.; Yiotakis, A.; Dive, V.
Potent and selective inhibition of zinc aminopeptidase A (EC 3.4.11.7, APA) by glutamyl aminophosphinic peptides: importance of glutamyl aminophosphinic residue in the P1 position
Biochemistry
39
1152-1155
2000
Mus musculus (P16406)
Iturrioz, X.; Vazeux, G.; Celerier, J.; Corvol, P.; Llorens-Cortes, C.
Histidine 450 plays a critical role in catalysis and, with Ca2+, contributes to the substrate specificity of aminopeptidase A
Biochemistry
39
3061-3068
2000
Mus musculus (P16406), Mus musculus
Iturrioz, X.; Rozenfeld, R.; Michaud, A.; Corvol, P.; Llorens-Cortes, C.
Study of asparagine 353 in aminopeptidase A: characterization of a novel motif (GXMEN) implicated in exopeptidase specificity of monozinc aminopeptidases
Biochemistry
40
14440-14448
2001
Mus musculus (P16406)
Rozenfeld, R.; Iturrioz, X.; Okada, M.; Maigret, B.; Llorens-Cortes, C.
Contribution of molecular modeling and site-directed mutagenesis to the identification of a new residue, glutamate 215, involved in the exopeptidase specificity of aminopeptidase A
Biochemistry
42
14785-14793
2003
Mus musculus (P16406)
Healy, D.P.
Regulation of aminopeptidase A activity by angiotensin II: Possible role in animal models of hypertension
Int. Congr. Ser.
1218
55-65
2001
Mus musculus (P16406)
-
Rozenfeld, R.; Iturrioz, X.; Maigret, B.; Llorens-Cortes, C.
Contribution of molecular modeling and site-directed mutagenesis to the identification of two structural residues, Arg-220 and Asp-227, in aminopeptidase A
J. Biol. Chem.
277
29242-29252
2002
Mus musculus (P16406)
David, C.; Bischoff, L.; Meudal, H.; Mothe, A.; De Mota, N.; DaNascimento, S.; Llorens-Cortes, C.; Fournie-Zaluski, M.C.; Roques, B.P.
Investigation of subsite preferences in aminopeptidase A (EC 3.4.11.7) led to the design of the first highly potent and selective inhibitors of this enzyme
J. Med. Chem.
42
5197-5211
1999
Mus musculus (P16406)
Iturrioz, X.; Reaux-Le Goazigo, A.; Llorens-Cortes, C.
Aminopeptidase inhibitors as anti-hypertensive drugs
Aminopetidases in Biology and Disease (Hooper, N. M. ; Lendaechel, U. , eds. ) Springer
2
229-250
2004
Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa
-
Adang, M.J.
Aminopeptidase A
Handbook of Proteolytic Enzymes (2nd Edition)
1
299-303
2004
Mus musculus (P16406)
-
Rozenfeld, R.; Muller, L.; El Messari, S.; Llorens-Cortes, C.
The C-terminal domain of aminopeptidase A is an intramolecular chaperone required for the correct folding, cell surface expression, and activity of this monozinc aminopeptidase
J. Biol. Chem.
279
43285-43295
2004
Mus musculus
Dijkman, H.B.; Assmann, K.J.; Steenbergen, E.J.; Wetzels, J.F.
Expression and effect of inhibition of aminopeptidase-A during nephrogenesis
J. Histochem. Cytochem.
54
253-262
2006
Mus musculus, Mus musculus BALB/c
Fournie-Zaluski, M.C.; Fassot, C.; Valentin, B.; Djordjijevic, D.; Reaux-Le Goazigo, A.; Corvol, P.; Roques, B.P.; Llorens-Cortes, C.
Brain renin-angiotensin system blockade by systemically active aminopeptidase A inhibitors: A potential treatment of salt-dependent hypertension
Proc. Natl. Acad. Sci. USA
101
7775-7780
2004
Mus musculus, Rattus norvegicus
Tsujimoto, M.; Goto, Y.; Maruyama, M.; Hattori, A.
Biochemical and enzymatic properties of the M1 family of aminopeptidases involved in the regulation of blood pressure
Heart Fail. Rev.
13
285-291
2007
Homo sapiens, Mus musculus, Rattus norvegicus
Bodineau, L.; Frugiere, A.; Marc, Y.; Claperon, C.; Llorens-Cortes, C.
Aminopeptidase A inhibitors as centrally acting antihypertensive agents
Heart Fail. Rev.
13
311-319
2008
Mus musculus, Rattus norvegicus
Bodineau, L.; Frugiere, A.; Marc, Y.; Inguimbert, N.; Fassot, C.; Balavoine, F.; Roques, B.; Llorens-Cortes, C.
Orally Active Aminopeptidase A Inhibitors Reduce Blood Pressure. A New Strategy for Treating Hypertension
Hypertension
51
1318-1325
2008
Mus musculus, Rattus norvegicus
Faber, F.; Gembardt, F.; Sun, X.; Mizutani, S.; Siems, W.E.; Walther, T.
Lack of angiotensin II conversion to angiotensin III increases water but not alcohol consumption in aminopeptidase A-deficient mice
Regul. Pept.
136
130-137
2006
Mus musculus
Claperon, C.; Rozenfeld, R.; Iturrioz, X.; Inguimbert, N.; Okada, M.; Roques, B.; Maigret, B.; Llorens-Cortes, C.
Asp218 participates with Asp213 to bind a Ca2+ atom into the S1 subsite of aminopeptidase A: a key element for substrate specificity
Biochem. J.
416
37-46
2008
Mus musculus (P16406), Mus musculus
Claperon, C.; Banegas-Font, I.; Iturrioz, X.; Rozenfeld, R.; Maigret, B.; Llorens-Cortes, C.
Identification of threonine 348 as a residue involved in aminopeptidase A substrate specificity
J. Biol. Chem.
284
10618-10626
2009
Mus musculus (P16406), Mus musculus
de Mota, N.; Iturrioz, X.; Claperon, C.; Bodineau, L.; Fassot, C.; Roques, B.P.; Palkovits, M.; Llorens-Cortes, C.
Human brain aminopeptidase A: biochemical properties and distribution in brain nuclei
J. Neurochem.
106
416-428
2008
Homo sapiens, Mus musculus
Morais, R.L.; Hilzendeger, A.M.; Visniauskas, B.; Todiras, M.; Alenina, N.; Mori, M.A.; Araujo, R.C.; Nakaie, C.R.; Chagas, J.R.; Carmona, A.K.; Bader, M.; Pesquero, J.B.
High aminopeptidase A activity contributes to blood pressure control in ob/ob mice by AT2 receptor-dependent mechanism
Am. J. Physiol. Heart Circ. Physiol.
312
H437-H445
2017
Mus musculus (P16406), Mus musculus, Mus musculus C57BL/6 (P16406)
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