Information on EC 3.4.16.2 - lysosomal Pro-Xaa carboxypeptidase

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

EC NUMBER
COMMENTARY hide
3.4.16.2
-
RECOMMENDED NAME
GeneOntology No.
lysosomal Pro-Xaa carboxypeptidase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
Cleavage of a -Pro-/-Xaa bond to release a C-terminal amino acid
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
CAS REGISTRY NUMBER
COMMENTARY hide
9075-64-3
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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
(des-Arg9)-bradykinin + H2O
?
show the reaction diagram
-
enzyme cleaves the -Pro7-/-Phe8-OH bond
-
-
?
1-dimethylaminonaphthalene-5-sulfonyl-Pro-Phe + H2O
1-dimethylaminonaphthalene-5-sulfonyl-Pro + Phe
show the reaction diagram
-
-
-
-
?
3-(2-furyl)acryloyl-peptide + H2O
?
show the reaction diagram
-
substrate used in the carboxypeptidase assay
-
-
?
4-phenylazobenzyloxycarbonyl-Pro-Leu + H2O
4-phenylazobenzyloxycarbonyl-Pro + Leu
show the reaction diagram
-
-
-
-
?
7-methoxycoumarin-4-acetyl-Pro-Pro-Lys + H2O
?
show the reaction diagram
-
-
-
?
Ala-Pro-4-nitroanilide + H2O
Ala-Pro + 4-nitroaniline
show the reaction diagram
alpha-melanocyte-stimulating hormone + H2O
?
show the reaction diagram
Angiotensin II + H2O
?
show the reaction diagram
angiotensin III + H2O
?
show the reaction diagram
-
-
-
-
?
angiotensin III + H2O
angiotensin 2-7 + phenylalanine
show the reaction diagram
-
mutant DELTA317-496 is able to carry out this reaction
-
-
?
dansyl-Pro-Phe + H2O
dansyl-Pro + Phe
show the reaction diagram
-
-
-
-
?
Gliadin + H2O
?
show the reaction diagram
-
enzyme is able to cleave gliadins, the major dietary proteins of Tenebrio molitor larvae
-
?
Gly-Pro-4-nitroanilide + H2O
Gly-Pro + 4-nitroaniline
show the reaction diagram
-
-
-
?
L-Ala-L-Pro 4-nitroanilide + H2O
L-Ala-L-Pro + 4-nitroaniline
show the reaction diagram
-
-
-
?
lariatin A + H2O
?
show the reaction diagram
-
C-terminal-lacking fragments of the anti-mycobacterial peptide lariatin A, isolated from a culture broth of Rhodococcus jostii, are obtained by hydrolysis using carboxypeptidase P and their anti-mycobacterial activities are evaluated. Lys17 is found to be essential for their antimicrobial activity
-
-
?
Myoglobin + H2O
?
show the reaction diagram
-
-
-
-
?
N-benzyloxycarbonyl-Gly-L-Pro 4-nitroanilide + H2O
N-benzyloxycarbonyl-Gly-L-Pro + 4-nitroaniline
show the reaction diagram
-
-
-
?
N-benzyloxycarbonyl-Gly-Pro-Phe + H2O
N-benzyloxycarbonyl-Gly-Pro + Phe
show the reaction diagram
-
-
-
-
?
N-benzyloxycarbonyl-L-Ala-L-Ala-L-Pro 4-nitroanilide + H2O
N-benzyloxycarbonyl-L-Ala-L-Ala-L-Pro + 4-nitroaniline
show the reaction diagram
-
-
-
?
N-benzyloxycarbonyl-L-Ala-L-Pro 4-nitroanilide + H2O
N-benzyloxycarbonyl-L-Ala-L-Pro + 4-nitroaniline
show the reaction diagram
-
-
-
?
N-benzyloxycarbonyl-L-Pro 4-nitroanilide + H2O
N-benzyloxycarbonyl-L-Pro + 4-nitroaniline
show the reaction diagram
-
-
-
?
N-benzyloxycarbonyl-L-Pro-L-Phe + H2O
N-benzyloxycarbonyl-L-Pro + L-Phe
show the reaction diagram
-
-
-
?
N-benzyloxycarbonyl-Pro-Ala + H2O
N-benzyloxycarbonyl-Pro + Ala
show the reaction diagram
N-benzyloxycarbonyl-Pro-Leu + H2O
N-benzyloxycarbonyl-Pro + Leu
show the reaction diagram
N-benzyloxycarbonyl-Pro-Phe + H2O
N-benzyloxycarbonyl-Pro + Phe
show the reaction diagram
N-benzyloxycarbonyl-Pro-Ser + H2O
N-benzyloxycarbonyl-Pro + Ser
show the reaction diagram
-
7% of the activity with angiotensin III
-
-
?
N-benzyloxycarbonyl-Pro-Val + H2O
N-benzyloxycarbonyl-Pro + Val
show the reaction diagram
prekallikrein + H2O
?
show the reaction diagram
-
-
-
?
saralasin + H2O
?
show the reaction diagram
-
-
-
-
?
YPRPIHPA + H2O
?
show the reaction diagram
-
using a peptidomic approach a single peptide YPRPIHPA is identified as a novel substrate for PRCP in human cerebrospinal fluid. The peptide YPRPIHPA is from the extracellular portion of human endothelin B receptor like protein 2
-
-
?
[des-Arg9]bradykinin + H2O
?
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
alpha-melanocyte-stimulating hormone + H2O
?
show the reaction diagram
YPRPIHPA + H2O
?
show the reaction diagram
-
using a peptidomic approach a single peptide YPRPIHPA is identified as a novel substrate for PRCP in human cerebrospinal fluid. The peptide YPRPIHPA is from the extracellular portion of human endothelin B receptor like protein 2
-
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
CaCl2
-
optimal activity at 0.01 mM
MgCl2
-
optimal activity at 1 mM
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(3R,4R)-4-[3-(4-chlorophenyl)-1H-pyrazol-5-yl]-1-(2,2-dimethylpropyl)-3-(4-fluorophenyl)piperidine
2-[4-[3-(4-fluorophenyl)-1-methyl-1H-pyrazol-5-yl]-1-(2-phenylethyl)piperidin-4-yl]pyridine
angiotensin I
-
inhibits the mutant DELTA317-496 in a dose-dependent manner
angiotensin II
Angiotensin III
-
inhibits the mutant DELTA317-496 in a dose-dependent manner
antipain
Benzoyl-D-Phe
-
-
benzyloxycarbonyl-Pro-Pro-aldehyde dimethyl acetate
-
IC50: 0.001 mM
-
benzyloxycarbonyl-Pro-Pro-aldehyde-dimethyl acetate
-
-
-
benzyloxycarbonyl-Pro-prolinal
-
IC50: 0.5 mM, inhibits hydrolysis of H-Gly-Pro-4-nitroanilide
Benzylsuccinic acid
-
-
bradykinin
bradykinin anti-PRCP
-
-
-
corn trypsin inhibitor
-
diisopropyl fluorophosphate
diisopropyl fluorophosphonate
ebelactone
-
noncompetitive
-
HgCl2
-
IC50: 0.5 mM
leupeptin
N-(9-fluorenyl)methoxycarbonyl-Ala-Pyr-CN
-
IC50: 50 nM
N-(9-fluorenyl)methoxycarbonyl-aminoacylpyrrolidine-2-nitrile
-
IC50: 0.1 mM
N-benzyloxycarbonyl-Pro-prolinal
N-benzyloxycarbonyl-prolyl-prolinal
-
the inhibition of PRCP activity by small molecule protease inhibitors administered peripherally or centrally decreased food intake in both wild-type and obese mice
NEM
-
3 mM, 30% inhibition
o-phenanthroline
-
-
p-Chloromercuriphenylsulfonic acid
-
1 mM, 15% inhibition
Pepstatin
phenylmethyl sulfonyl fluoride
-
3 mM
phenylmethylsulfonyl fluoride
Potato carboxypeptidase inhibitor
-
protease inhibitors of the blood plasma
-
-
-
t-butyl carbamate-prolyl-prolinal
-
the inhibition of PRCP activity by small molecule protease inhibitors administered peripherally or centrally decreased food intake in both wild-type and obese mice
Z-Pro-prolinal
-
-
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl](4-[(1Z)-1-[(2,5-dichlorophenyl)amino]-3-iminobut-1-en-1-yl]piperidin-1-yl)methanone
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl](4-[(1Z)-1-[(3-chloro-4-fluorophenyl)amino]-3-iminoprop-1-en-1-yl]piperidin-1-yl)methanone
[4-[1-(3-chloro-4-fluorophenyl)-1H-pyrazol-5-yl]piperidin-1-yl][(1R,2R,4S)-2-(2,4-difluorophenyl)-4-(dimethylamino)-4-methylcyclopentyl]methanone
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
As2O3
-
when seedlings are raised under 25 and 50 microM As2O3 in the medium, the activity level of carboxypeptidase is enhanced
thrombin
-
-
-
additional information
-
in cells, treated with 30 nM dexamethasone plus 1 nM DAMGO ([D-Ala2, N-Me-Phe4, Gly5-ol]-Enkephalin), the prolyl-carboxypeptidase gene is up-regulated
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.5 - 3.1
Ala-Pro-4-nitroanilide
0.34 - 1
angiotensin II
2
Angiotensin III
-
-
0.26
benzyloxycarbonyl-Pro-Leu
-
-
4
Gly-Pro-4-nitroanilide
-
pH 5.5, 37°C
0.157
L-Ala-L-Pro 4-nitroanilide
pH 5.6, 30°C
0.1 - 0.13
Myoglobin
-
0.147
N-benzyloxycarbonyl-Gly-L-Pro 4-nitroanilide
pH 5.6, 30°C
0.34
N-benzyloxycarbonyl-L-Ala-L-Ala-L-Pro 4-nitroanilide
pH 5.6, 30°C
0.095
N-benzyloxycarbonyl-L-Ala-L-Pro 4-nitroanilide
pH 5.6, 30°C
0.17
N-benzyloxycarbonyl-L-Pro 4-nitroanilide
pH 5.6, 30°C
4.7
N-benzyloxycarbonyl-L-Pro-L-Ala
-
-
0.77 - 1.3
N-benzyloxycarbonyl-Pro-Phe
0.0000067 - 0.000017
prekallikrein
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.3 - 1.1
Myoglobin
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
210
YPRPIHPA
Homo sapiens
-
determined by an in vitro assay using human recombinant PRCP
160396
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0037
N-benzyloxycarbonyl-Pro-prolinal
pH 5.6, 30°C
0.0000004 - 0.0000009
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl](4-[(1Z)-1-[(2,5-dichlorophenyl)amino]-3-iminobut-1-en-1-yl]piperidin-1-yl)methanone
0.0000005 - 0.0000014
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl](4-[(1Z)-1-[(3-chloro-4-fluorophenyl)amino]-3-iminoprop-1-en-1-yl]piperidin-1-yl)methanone
0.0000003 - 0.0000013
[4-[1-(3-chloro-4-fluorophenyl)-1H-pyrazol-5-yl]piperidin-1-yl][(1R,2R,4S)-2-(2,4-difluorophenyl)-4-(dimethylamino)-4-methylcyclopentyl]methanone
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000066 - 0.00018
(3R,4R)-4-[3-(4-chlorophenyl)-1H-pyrazol-5-yl]-1-(2,2-dimethylpropyl)-3-(4-fluorophenyl)piperidine
0.0000007 - 0.0000033
2-[4-[3-(4-fluorophenyl)-1-methyl-1H-pyrazol-5-yl]-1-(2-phenylethyl)piperidin-4-yl]pyridine
1
angiotensin I
Homo sapiens
-
-
0.002 - 3
angiotensin II
0.002 - 0.05
antipain
0.001
benzyloxycarbonyl-Pro-Pro-aldehyde dimethyl acetate
Homo sapiens
-
IC50: 0.001 mM
-
0.5
benzyloxycarbonyl-Pro-prolinal
Homo sapiens
-
IC50: 0.5 mM, inhibits hydrolysis of H-Gly-Pro-4-nitroanilide
0.007
Benzylsuccinic acid
Homo sapiens
-
-
0.1 - 3
bradykinin
0.00004 - 0.0001
corn trypsin inhibitor
-
0.00005
diisopropyl fluorophosphonate
Homo sapiens
-
IC50: 50 nM
0.5
HgCl2
Homo sapiens
-
IC50: 0.5 mM
0.8
leupeptin
Homo sapiens
-
IC50: 0.8 mM, inhibits hydrolysis of Gly-Pro-4-nitroanilide
0.00005
N-(9-fluorenyl)methoxycarbonyl-Ala-Pyr-CN
Homo sapiens
-
IC50: 50 nM
0.1
N-(9-fluorenyl)methoxycarbonyl-aminoacylpyrrolidine-2-nitrile
Homo sapiens
-
IC50: 0.1 mM
0.6
phenylmethylsulfonyl fluoride
Homo sapiens
-
IC50: 0.6 mM
0.00005
Potato carboxypeptidase inhibitor
Homo sapiens
-
-
-
0.0000003 - 0.0000004
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl](4-[(1Z)-1-[(2,5-dichlorophenyl)amino]-3-iminobut-1-en-1-yl]piperidin-1-yl)methanone
0.0000002 - 0.0000003
[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl](4-[(1Z)-1-[(3-chloro-4-fluorophenyl)amino]-3-iminoprop-1-en-1-yl]piperidin-1-yl)methanone
0.0000002 - 0.0000003
[4-[1-(3-chloro-4-fluorophenyl)-1H-pyrazol-5-yl]piperidin-1-yl][(1R,2R,4S)-2-(2,4-difluorophenyl)-4-(dimethylamino)-4-methylcyclopentyl]methanone
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.51
-
-
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4
-
carboxypeptidase P (and in combiantion with carboxypeptidase Y) is used to determine the C-terminal amino acid sequence of recombinant Hirudin Variant 3, HV3
4.5 - 5.5
5
-
carboxypeptidase assay
5.5
assay at
5.8
-
assay at
7.5
-
carboxypeptidase assay
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
2 - 6
-
hydrolysis of myoglobin by CPP is carried out in acid conditons on the QCM
2.5 - 5
-
hydrolysis of myoglobin in the bulk solution
4.5 - 7
6.8 - 7.4
-
more than 75% of maximal activity at pH 6.8 and pH 7.4
7 - 9
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
-
carboxypeptidase assay
additional information
assay at room temperature
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
9.9
-
predicted
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
aortic aneurysm and normal aorta
Manually annotated by BRENDA team
-
pancreatic cancer cell line
Manually annotated by BRENDA team
-
greatest level of signals are detected in the cerebral cortex with very strong labeling in the cingulate and piriform cortex. Other areas of the cortex show moderate signal intensity
Manually annotated by BRENDA team
-
embryonic tissue
Manually annotated by BRENDA team
-
used for transfection
Manually annotated by BRENDA team
-
within the limbic system, strong signal is detected in the hippocampus and in the amygdaloid complex
Manually annotated by BRENDA team
anterior midgut of larvae
Manually annotated by BRENDA team
-
RNA is extracted from leukocytes
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
expression of PRCP protein or kallikrein mRNA expression is significantly inhibited in the right kidneys and mesenteric arteries of hypertensive rats. Expression is significantly increased after treatment with rutaecarpine or lorsartan
Manually annotated by BRENDA team
-
enzyme mRNA detected in the zona incerta and the ventral tegmental area
Manually annotated by BRENDA team
-
pancreatic cancer cell line
Manually annotated by BRENDA team
-
prolylcarboxypeptidase transcript levels are compared
Manually annotated by BRENDA team
-
pancreatic cancer cell line
Manually annotated by BRENDA team
-
foreskin fibroblast
Manually annotated by BRENDA team
-
root of seedling
Manually annotated by BRENDA team
-
shoot of seedling
Manually annotated by BRENDA team
-
strong expression
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
the 37-kDa active form of the protein is secreted into the extracellular matrix
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37000
-
active form, determined by SDS-PAGE and Western blot analysis
40000
-
mutant DELTA317-496
45000
-
x * 45000 + x * 66500, SDS-PAGE in presence of 2-mercaptoethanol
50000
-
pro-CPA6, determined by SDS-PAGE and Western blot analysis
51043
-
x * 51043, calculation from nucleotide sequence
52000
-
predicted from cDNA
53554
2 * 53554, mass spectrometry of mature protein
55800
-
-
58000
-
x * 58000, SDS-PAGE
60000
-
-
66500
-
x * 45000 + x * 66500, SDS-PAGE in presence of 2-mercaptoethanol
83000
-
4 * 83000, SDS-PAGE
105000
gel filtration
110000
-
gel filtration
115000
-
gel filtration
210000
-
non-denaturing PAGE
330000
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
2 * 53554, mass spectrometry of mature protein
homodimer
-
-
tetramer
-
4 * 83000, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystallization of glycosylated human PrCP from stably transformed CHO cells is described. Purified PrCP yields crystals belonging to space group R32, with unit-cell parameters a = b = 181.14, c = 240.13 A, that diffract to better than 2.8 A resolution
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8 - 11
-
37°C, 60 min, 20% loss of activity
36274
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
35
-
pH 8.0, 60 min, 20% loss of activity
37
-
half-life: 240 min
70
-
15 min, 90% loss of activity
95
-
3 min, complete loss of activity
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
purchased from TaKaRa Bio Inc. Japan, lot no. 1921, 2001, 2031
-
recombinant
-
soluble proteins are precipitated from the supernatant of homogenized plant material
-
using Ni-affinity chromatography
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a cDNA fragment encoding human pro-CPA6 is subcloned into the pcDNA3.1 vector; expressed in AT-20 cells
-
cDNA cloned in pMT/BIP/V5-HIS-C, transfected into Schneider insect cells
-
cloned in pMT/BIP/V5-HIS-C, transfected into Scheider insect cells
-
expressed in Schneider insect cells
-
overexpression in Chineses hamster ovary cells. CHO cells are transfected with full-length prolylcarboxypeptidase under the control of a cytomegalovirus promoter. CHO recombinant prolylcarboxypeptidase is expressed as a fusion protein with COOH-terminal enhanced green fluorescence protein. Overexpression in the external membrane
-
PrCP is cloned with an N-terminal FLAG tag and a C-terminal heptahistidine tag under the trypsin II signal sequence in pcDNA5/FRT and expressed in stably transfected CHO cells
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression of PRC is significantly increased in the right kidneys and mesenteric arteries of hypertensive rats after treatment with rutaecarpine or lorsartan
expression of PRCP protein or kallikrein mRNA expression is significantly inhibited in the right kidneys and mesenteric arteries of hypertensive rats
PRCP is critical to the maintenance of HUVEC cells, and its upregulation contributes to the risk of developing inflammation
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
DELTA317-496
-
an N-terminal truncated form, lacking 179 N-terminal residues of PRCP is constructed. The circular dichroism spectrum of the truncated mutant illustrates that it is structured with significant helical content as indicated by local minima at 220 and 208 nm. The main products of angiotensin III metabolized by the truncated mutant is angiotensin 2-7 plus phenylalanine as determined by LC-MS. Angiotensin I blockes the metabolism of angiotensin III by the truncated mutant. Km (mM) (Ala-Pro-4-nitroanilide) lower compared to wild-type
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
-
enzymatic sequencing by MALDI-MS combined with carboxypeptidase cleavage
medicine