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Information on EC 3.4.13.9 - Xaa-Pro dipeptidase and Organism(s) Homo sapiens and UniProt Accession P12955
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3.4.13.9 Xaa-Pro dipeptidaseSpecify your search results
Word Map
- 3.4.13.9
- collagen
- dipeptides
- ulcer
- hydroxyproline
- gly-pro
-
opaas
- soman
-
exopeptidase
-
proline-containing
- prolinase
-
map-kinases
- paraoxonase
- dfp
- igf-ir
- alteromonas
- erk1
-
splenomegaly
- sarin
- medicine
- beta1-integrin
- analysis
- diagnostics
- drug development
- degradation
- biotechnology
- food industry
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
Reaction Schemes
hydrolysis of Xaa-/-Pro dipeptides; also acts on aminoacyl-hydroxyproline analogs. No action on Pro-Pro
hydrolysis of Xaa-/-Pro dipeptides; also acts on aminoacyl-hydroxyamine analogues. No action on Pro-Pro
Synonyms
prolidase, serum prolidase, peptidase d, prolidase i, organophosphorus acid anhydrolase, proline dipeptidase, prolidase ii, imidodipeptidase, quiescent cell proline dipeptidase, prolyl dipeptidase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
dipeptidase, proline
-
-
-
-
gamma-peptidase
-
-
-
-
imidodipeptidase
-
-
-
-
peptidase D
prolidase
Proline dipeptidase
-
-
-
-
quiescent cell proline dipeptidase
X-Pro dipeptidase
-
-
-
-
additional information
peptidase D
-
-
-
-
prolidase
-
-
-
-
prolidase
-
-
prolidase
-
prolidase hydrolyses dipeptides containing C-terminal proline and hydroxyproline
additional information
-
enzyme belongs to the methionyl amino peptidase family M24, fomerly EC 3.4.3.7
additional information
-
enzyme belongs to the methionyl amino peptidase family M24, fomerly EC 3.4.3.7
additional information
-
enzyme belongs to the methionyl amino peptidase family M24, fomerly EC 3.4.3.7
additional information
-
enzyme belongs to the methionyl amino peptidase family M24, fomerly EC 3.4.3.7
additional information
-
enzyme belongs to the methionyl amino peptidase family M24, fomerly EC 3.4.3.7
additional information
-
enzyme belongs to the methionyl amino peptidase family M24, fomerly EC 3.4.3.7
additional information
-
prolidase belongs to a subclass of metallopeptidases that contain a dinuclear active-site metal cluster, and further into a smaller class of metalloenzymes known as the pita-bread enzymes
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hydrolysis of Xaa-/-Pro dipeptides; also acts on aminoacyl-hydroxyproline analogs. No action on Pro-Pro
hydrolysis of Xaa-/-Pro dipeptides; also acts on aminoacyl-hydroxyamine analogues. No action on Pro-Pro
mechanism of substrate specificity and catalysis, overview
-
hydrolysis of Xaa-/-Pro dipeptides; also acts on aminoacyl-hydroxyproline analogs. No action on Pro-Pro
catalytic mechanism
-
hydrolysis of Xaa-/-Pro dipeptides; also acts on aminoacyl-hydroxyproline analogs. No action on Pro-Pro
cleaves imidodipeptides containing C-terminal proline providing a large amount of proline for collagen resynthesis
-
hydrolysis of Xaa-/-Pro dipeptides; also acts on aminoacyl-hydroxyproline analogs. No action on Pro-Pro
the enzyme cleaves N-terminal Xaa-Pro dipeptides from proteins
-
hydrolysis of Xaa-/-Pro dipeptides; also acts on aminoacyl-hydroxyproline analogs. No action on Pro-Pro
catalytic mechanism and active site structure
-
CAS REGISTRY NUMBER
COMMENTARY
9025-32-5
-
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
Gly-L-Pro + H2O
Gly + L-Pro
-
-
667109, 667350, 667803, 668271, 668292, 670953, 695528, 695908, 697476, 697568, 697758, 699153, 699184, 700612, 710614
-
-
?
Gly-Pro-4-trifluoromethylcoumarin-7-amide + H2O
Gly + Pro + 7-amino-4-trifluoromethylcoumarin
-
-
-
-
?
Ala-Pro-amino-4-trifluoromethylcoumarin + H2O
alanine + Pro-4-trifluoromethylcoumarin
-
-
-
?
Ala-Pro-amino-4-trifluoromethylcoumarin + H2O
alanine + Pro-4-trifluoromethylcoumarin
-
-
-
?
Gly-Pro + H2O
Gly + Pro
-
-
-
-
?
melphalan + H2O
?
-
prolidase-dependence of prodrug cytotoxicity in the cell lines compared to that of the parent drug, melphalan, overview
-
-
?
prophalan-D + H2O
?
-
the D-proline prodrug of melphalan, bioactivation and uptake of prolidase-targeted proline prodrugs, prolidase-dependence of prodrug cytotoxicity in the cell lines compared to that of the parent drug, melphalan, overview
-
-
?
prophalan-L + H2O
?
-
the L-proline prodrug of melphalan, bioactivation and uptake of prolidase-targeted proline prodrugs, prolidase-dependence of prodrug cytotoxicity in the cell lines compared to that of the parent drug, melphalan, overview
-
-
?
additional information
?
-
human prolidase is the only metalloenzyme among the peptidases that cleaves the iminodipeptides containing a proline or hydroxyproline residue at the C-terminal end
-
-
?
additional information
?
-
-
human prolidase is the only metalloenzyme among the peptidases that cleaves the iminodipeptides containing a proline or hydroxyproline residue at the C-terminal end
-
-
?
additional information
?
-
-
cleaves imidodipeptides with C-terminal proline or hydroxyproline
-
?
additional information
?
-
-
the acive enzyme form is N-glycosylated, unglycosylated enzyme is not catalytically active
-
?
additional information
?
-
-
the enzyme is involved in collagen metabolism
-
?
additional information
?
-
-
the enzyme is involved in collagen metabolism, enzyme activity is regulated through the beta1 integrin receptor
-
?
additional information
?
-
-
the enzyme plays an important role in recycling of proline for collagen synthesis and cell growth, regulation by phosphorylation and dephosphorylation
-
?
additional information
?
-
-
substrate specificity of wild-type and mutant enzymes, overview
-
-
?
additional information
?
-
-
enzyme additionally hydrolyzes organophosphorous compounds like soman
-
-
?
additional information
?
-
-
enzyme additionally hydrolyzes organophosphorous compounds such as soman
-
-
?
additional information
?
-
-
alpha-ketoglutarate increases activities of prolidase, which is known to play an important role in collagen metabolism, in fibroblasts, N-benzyloxycarbonyl-L-proline, a prolidase inhibitor, inhibits procollagen synthesis by alpha-ketoglutarate in fibroblasts, alpha-ketoglutarate diminishes UVB-induced wrinkle formation by increasing collagen production, through a pathway that involves prolidase activation, regulation, overview
-
-
?
additional information
?
-
-
interleukin-1beta action and inhibition, resulting in increase in beta1-integrin receptor, NF-kappaB expressions, and increase in phosphorylation of FAK, does deregulate the collagen metabolism, but does not influence the prolidase activity, while metalloproteinase MMP-2 and MMP-9 activities are activated, overview
-
-
?
additional information
?
-
-
prolidase deficiency causes a rare autosomal recessive disease, characterized by a wide range of clinical outcomes, including severe skin lesions, mental retardation, and infections of the respiratory tract
-
-
?
additional information
?
-
-
prolidase is involved in the final stage of degradation in collagen catabolism
-
-
?
additional information
?
-
-
prolidase plays an important role in enhancement of collagen biosynthesis at post-translational level
-
-
?
additional information
?
-
-
prolidase, a specific iminopeptidase involved in collagen turnover, is especially active in growing tissues, the final step of collagen degradation is mediated by prolidase, the cytosolic enzyme specifically splits iminopeptides with C-terminal proline or hydroxyproline, which together contribute 21% of collagen
-
-
?
additional information
?
-
-
the enzyme catalyzes the final step of collagen degradation and plays an important role in collagen biosynthesis
-
-
?
additional information
?
-
-
the enzyme is relevant in the latest stage of protein catabolism, particularly of those molecules rich in imino acids such as collagens, thus being involved in matrix remodelling, overview, prolidase has an antitoxic effect against some organophosphorus molecules, can be used in dietary industry as bitterness reducing agent and is used as target enzyme for specific melanoma prodrug activation, prolidase deficiency is a rare recessive disorder caused by mutations in the prolidase gene and characterized by severe skin lesions, overview
-
-
?
additional information
?
-
-
the enzyme plays an important role in the recycling of proline from imidodipeptides, mostly derived from degradation products of collagen, for resynthesis of collagen and other proline-containing proteins, prolidase-dependent regulation of collagen biosynthesis, pathogenic mechanisms in enzyme deficiency, overview
-
-
?
additional information
?
-
-
prolidase is a Mn2+-dependent exo- or dipeptidase that cleaves imidodipeptides containing C-terminal proline or hydroxyproline, substrate specificity of native and recombinant enzymes, molecular modeling, overview
-
-
?
additional information
?
-
-
prolidase is an unusual metalloenzyme that cleaves the iminodipeptides containing a proline or hydroxyproline residue at the C-terminal end, it is a dipeptidase able to hydrolyse the peptide bond in dipeptides containing respectively a N- or C-terminal proline or hydroxyproline residue, overview, recombinant human prolidase expressed in Pichia pastoris catalyzes the hydrolysis of organophosphorus compounds as well as the digestion of Gly-Pro dipeptides
-
-
?
additional information
?
-
-
specific activities with melphalan and prodrugs in cancer cell lines, overview
-
-
?
additional information
?
-
-
substrate specificity, prolidase is a cytosolic imidodipeptidase, which specifically splits imidodipeptides with C-terminal proline or hydroxyproline, overview
-
-
?
additional information
?
-
-
prolidases are specific for dipeptides with proline in the trans configuration in the P1' position and nonpolar residues in the P1 position
-
-
?
additional information
?
-
-
prolidase hydrolyses dipeptides containing proline or hydroxyproline as the C-terminal amino acid
-
-
?
additional information
?
-
-
prolidase is a exopeptidase that cleaves iminodipeptides containing C-terminal proline or hydroxyproline
-
-
?
additional information
?
-
-
prolidase is a manganese-requiring homodimeric iminodipeptidase, which releases carboxy-terminal proline or hydroxyproline from oligopeptides
-
-
?
additional information
?
-
-
prolidase is an exopeptidase cleaving C-terminally proline and hydroxyproline from iminodipeptides
-
-
?
additional information
?
-
-
prolidase is an iminodipeptidase, which releases C-terminal proline or hydroxyproline from oligopeptides
-
-
?
additional information
?
-
-
the enzyme is also active with diisopropyl phosphorofluoridate, an organophosphorus nerve reagent
-
-
?
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
melphalan + H2O
?
-
prolidase-dependence of prodrug cytotoxicity in the cell lines compared to that of the parent drug, melphalan, overview
-
-
?
prophalan-D + H2O
?
-
the D-proline prodrug of melphalan, bioactivation and uptake of prolidase-targeted proline prodrugs, prolidase-dependence of prodrug cytotoxicity in the cell lines compared to that of the parent drug, melphalan, overview
-
-
?
prophalan-L + H2O
?
-
the L-proline prodrug of melphalan, bioactivation and uptake of prolidase-targeted proline prodrugs, prolidase-dependence of prodrug cytotoxicity in the cell lines compared to that of the parent drug, melphalan, overview
-
-
?
additional information
?
-
-
the enzyme is involved in collagen metabolism
-
?
additional information
?
-
-
the enzyme is involved in collagen metabolism, enzyme activity is regulated through the beta1 integrin receptor
-
?
additional information
?
-
-
the enzyme plays an important role in recycling of proline for collagen synthesis and cell growth, regulation by phosphorylation and dephosphorylation
-
?
additional information
?
-
-
alpha-ketoglutarate increases activities of prolidase, which is known to play an important role in collagen metabolism, in fibroblasts, N-benzyloxycarbonyl-L-proline, a prolidase inhibitor, inhibits procollagen synthesis by alpha-ketoglutarate in fibroblasts, alpha-ketoglutarate diminishes UVB-induced wrinkle formation by increasing collagen production, through a pathway that involves prolidase activation, regulation, overview
-
-
?
additional information
?
-
-
interleukin-1beta action and inhibition, resulting in increase in beta1-integrin receptor, NF-kappaB expressions, and increase in phosphorylation of FAK, does deregulate the collagen metabolism, but does not influence the prolidase activity, while metalloproteinase MMP-2 and MMP-9 activities are activated, overview
-
-
?
additional information
?
-
-
prolidase deficiency causes a rare autosomal recessive disease, characterized by a wide range of clinical outcomes, including severe skin lesions, mental retardation, and infections of the respiratory tract
-
-
?
additional information
?
-
-
prolidase is involved in the final stage of degradation in collagen catabolism
-
-
?
additional information
?
-
-
prolidase plays an important role in enhancement of collagen biosynthesis at post-translational level
-
-
?
additional information
?
-
-
prolidase, a specific iminopeptidase involved in collagen turnover, is especially active in growing tissues, the final step of collagen degradation is mediated by prolidase, the cytosolic enzyme specifically splits iminopeptides with C-terminal proline or hydroxyproline, which together contribute 21% of collagen
-
-
?
additional information
?
-
-
the enzyme catalyzes the final step of collagen degradation and plays an important role in collagen biosynthesis
-
-
?
additional information
?
-
-
the enzyme is relevant in the latest stage of protein catabolism, particularly of those molecules rich in imino acids such as collagens, thus being involved in matrix remodelling, overview, prolidase has an antitoxic effect against some organophosphorus molecules, can be used in dietary industry as bitterness reducing agent and is used as target enzyme for specific melanoma prodrug activation, prolidase deficiency is a rare recessive disorder caused by mutations in the prolidase gene and characterized by severe skin lesions, overview
-
-
?
additional information
?
-
-
the enzyme plays an important role in the recycling of proline from imidodipeptides, mostly derived from degradation products of collagen, for resynthesis of collagen and other proline-containing proteins, prolidase-dependent regulation of collagen biosynthesis, pathogenic mechanisms in enzyme deficiency, overview
-
-
?
additional information
?
-
-
prolidases are specific for dipeptides with proline in the trans configuration in the P1' position and nonpolar residues in the P1 position
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mn2+
the protein can host two metal ions in the active site of each constituent monomer, two different kinds of metals, Mn and Zn can be simultaneously present in the protein active sites with the protein partially maintaining its enzymatic activity. Dimeric metalloenzyme, one of the two active sites is occupied by two Zn ions and the second one by one Zn and one Mn ion, in both dinuclear units a histidine residue is bound to a Zn ion, binding structure, overview
Zn2+
the protein can host two metal ions in the active site of each constituent monomer, two different kinds of metals, Mn and Zn can be simultaneously present in the protein active sites with the protein partially maintaining its enzymatic activity. Dimeric metalloenzyme, one of the two active sites is occupied by two Zn ions and the second one by one Zn and one Mn ion, in both dinuclear units a histidine residue is bound to a Zn ion, binding structure, overview
Co2+
Mn2+
Na+
-
the enzyme contains five Na+ ions, four organized in two dinuclear centres and one located in an external position of the homodimer, each subunit contains two ions Na+, binding structure, overview
additional information
Mn2+
-
metalloenzyme, required for activity, each subunit contains two ions Mn2+, binding structure, overview
Mn2+
-
metalloenzyme, required for activity, the active site Mn2+ cation is simultaneously ligated to the prolyl carboxyl group and the amido oxygen of the preceding residue of the trans X-Pro dipeptides
Mn2+
-
required, plays an important role in the activation and functional regulation of the enzyme
additional information
determination of enzyme samples metal contents, overview
additional information
-
determination of enzyme samples metal contents, overview
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
betulinic acid
-
i.e. 3beta-hdroxy-lup-20(29)-en-28-oic acid, inhibits the enzyme and is involved in anti-angiogenesis due to further inhibition of expression and decrease in expressions of alpha1 and alpha2 integrins, hypoxia-inducible factor 1, HIF-1, and vascular endothelial cell growth factor, detailed overview
Colchicine
-
colchicine has a slight inhibiting effect on prolidase activity for L-Val-L-Pro, the activity reaches its highest inhibition percentage of 59% at 2.0 mM
D,L-homocysteine-thiolactone
-
inhibits the activities of isozymes prolidase I and II in a concentration-dependent manner
daunorubicin
-
a cytotoxic anthracycline, inhibits the enzyme and collagen biosynthesis, inhibition mechanism might act via chelating of essential Mn2+ ions, more effective than doxorubicin, also inhibits DNA synthesis
DL-homocysteine
-
slightly activates at concentrations of 1-20 mM, inhibitory at over 30 mM, overview
DL-homocysteine thiolactone
-
activates at concentrations of 1-30 mM, inhibitory at over 50 mM, overview
DL-methionine
-
activates at concentrations of 1-30 mM, inhibitory at over 50 mM, overview
doxorubicin
-
a cytotoxic anthracycline, inhibits the enzyme and collagen biosynthesis, inhibition mechanism might act via chelating of essential Mn2+ ions, less effective than daunorubicin, also inhibits DNA synthesis
doxycyclin
-
induces down-regulation of the enzyme as a post-translational event
echistatin
-
treatment of cells results in inhibition of collagen production and enzyme activity and expression
-
L-isoleucine
-
inhibitory to enzyme isoform prolidase I, activating isoform prolidase II
L-leucine
-
inhibitory to enzyme isoform prolidase I, activating isoform prolidase II
L-valine
-
inhibitory to enzyme isoform prolidase I, activating isoform prolidase II
melanin
-
30% inhibition at 0.1 mg/ml, reverses inhibition of prolidase by netilmicin
paracetamol
-
mechanism of PLD inhibition by paracetamol is noncompetitive inhibition
N-Benzyloxycarbonyl-L-proline
-
90% inhibition after incubation of cell extracts at a 1:1 ratio of inhibitor to substrate Gly-L-Pro. Long-term incubation of fibroblasts with inhibitor causes mitochondria depolarization and increased cellular death
N-Benzyloxycarbonyl-L-proline
-
competitive, 60-83% inhibition levels of the enzyme from different cancer cell lines, overview
additional information
-
effects of sulfated amino acids on enzyme-deficient erythrocytes, overview
-
additional information
-
carmustine does not inhibit MCF-7 cells prolidase activity
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(4S)-4-ethyl-4-hydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione
-
deregulates the collagen metabolism and strongly induces inhibition of collagen synthesis, but activates the enzyme accompanied by increase in the expression of b1 integrin receptor and some b1 integrin-dependent signalling proteins, e.g. Sos, MAPK ERK1and ERK2, and transcription factor NF-kB, the specific MEK/ERK inhibitor UO126 inhibits campthotecin-induced up-regulation of prolidase activity
apigenin-7-O-glucuronide
-
stimulates the enzyme and collagen biosynthesis in osteogenesis imperfecta type I cells, overview
Colchicine
-
colchicine enhances PLD activity for Gly-L-Pro and L-Leu-L-Pro, the highest enhancement of PLD on Gly-L-Pro is 141% at 0.01 mM
D,L-ethionine
-
enhances the activity of isozyme prolidase I, D,L-ethionine strongly enhances the activity of isozyme prolidase II compared with L-ethionine
L-isoleucine
-
inhibitory to enzyme isoform prolidase I, activating isoform prolidase II
L-leucine
-
inhibitory to enzyme isoform prolidase I, activating isoform prolidase II
L-valine
-
inhibitory to enzyme isoform prolidase I, activating isoform prolidase II
MnCl2
-
stimulation of activity against substrates L-Pro-Gly, L-Pro-L-Glu, L-Pro-L-Leu, L-Pro-L-Ser, and L-Pro-L-Phe, inhibitory to hydrolysis of substrates L-Pro-L-Ala, L-Pro-L-Val, L-Pro-L-Met, and L-Pro-L-Asp
N-[N'-(2-bromoethyl)-N'-nitrosocarbamoyl]-L-proline
-
significantly increases MCF-7 cells prolidase activity, when used at 0.05-0.25 mM concentrations
N-[N'-(2-chloroethyl)-N'-nitrosocarbamoyl]-L-proline
-
significantly increases MCF-7 cells prolidase activity, when used at 0.05-0.25 mM concentrations
N-[N'-(3-chloropropyl)-N'-nitrosocarbamoyl]-L-proline
-
significantly increases MCF-7 cells prolidase activity, when used at 0.05-0.25 mM concentrations
N-[N'-(4-bromophenyl)-N'-nitrosocarbamoyl]-L-proline
-
significantly increases MCF-7 cells prolidase activity, when used at 0.05-0.25 mM concentrations
NO
-
NO stimulate both prolidase activity and collagen biosynthesis in fibroblasts, increase in the enzyme activity is due to increase in the enzyme phosphorylation on serine/threonine residue
pectolinarin
-
stimulates the enzyme and collagen biosynthesis in osteogenesis imperfecta type I cells, overview
thrombin
-
treatment of cells results in enhancement of collagen production and enzyme activity and expression, accompanied by raise in expression of focal adhesion kinase pp125 and mitogen-activated protein kinases
-
D,L-homocysteine
-
enhances the activity of isozyme prolidase I at low concentration
D,L-methionine
-
slightly enhances the activity of isozyme prolidase I at low concentration
D,L-methionine
-
the activity of isozyme prolidase II against L-Met-L-Pro is enhanced by D,L-methionine
D-methionine
-
the activity of isozyme prolidase I against Gly-L-Pro is strongly enhanced by D-methionine
D-methionine
-
the activity of isozyme prolidase II against L-Met-L-Pro is enhanced by D-methionine
glycine
-
activation of activity against substrates L-Pro-L-Ala, L-Pro-L-Val, L-Pro-L-Met, and L-Pro-L-Asp
L-methionine
-
slightly enhances the activity of isozyme prolidase I at low concentration
L-methionine
-
the activity of isozyme prolidase II against L-Met-L-Pro is enhanced by L-methionine
additional information
-
phosphorylation at four S109, S134, S198, S236, one T86, and two Y117, Y124 putative sites for phosphorylation, mediated respectively by Mapk pathway and NO/cGMP signaling, upregulate prolidase activity
-
additional information
-
prolidase activity is dependent on the interaction of collagen with the beta1-integrin receptor subunit
-
additional information
-
N-acetyl-L-methionine has no effect on activity of isozymes prolidase I and prolidase II
-
additional information
-
increased enzyme activity in patients with casculogenic erectile dysfunction, highest enzyme activity in patients with arterial insufficiency
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2.13
Gly-L-Pro
-
in the presence of 0.1 mM colchicine, 1.0 mM Mn2+, in 30 mM phosphate buffer (pH 7.5) 5.0 mM Ru(bpy)32+, at 37°C
6.23
Gly-L-Pro
-
in the absence of colchicine, 1.0 mM Mn2+, in 30 mM phosphate buffer (pH 7.5) 5.0 mM Ru(bpy)32+, at 37°C
2.88 - 2.9
Gly-Pro
-
prolidase I from normal human and mother of patient with prolidase deficiency
0.395
L-Leu-L-Pro
-
in the presence of 0.1 mM colchicine, 1.0 mM Mn2+, in 30 mM phosphate buffer (pH 7.5) 5.0 mM Ru(bpy)32+, at 37°C
0.628
L-Leu-L-Pro
-
in the absence of colchicine, 1.0 mM Mn2+, in 30 mM phosphate buffer (pH 7.5) 5.0 mM Ru(bpy)32+, at 37°C
4.43
L-Met-L-Pro
-
pH 7.8, 37°C, presence of 20 mM glycine, enzyme from patient with enzyme deficiency
5.48
L-Met-L-Pro
-
pH 7.8, 37°C, presence of 20 mM L-valine, enzyme from patient with enzyme deficiency
6.16
L-Met-L-Pro
-
pH 7.8, 37°C, presence of 20 mM D-valine, enzyme from patient with enzyme deficiency
8.6
L-Pro-Gly
-
pH 7.8, 37°C, presence of 0.1 mM MnCl2 plus 20 mM glycine, enzyme from patient with enzyme deficiency
9.7
L-Pro-Gly
-
pH 7.8, 37°C, presence of 0.1 mM MnCl2, enzyme from patient with enzyme deficiency
16.7
L-Pro-Gly
-
pH 7.8, 37°C, presence of 20 mM glycine, enzyme from patient with enzyme deficiency
4.2
L-Pro-L-Met
-
pH 7.8, 37°C, presence of 20 mM glycine, enzyme from patient with enzyme deficiency
5
L-Pro-L-Met
-
pH 7.8, 37°C, presence of 0.1 mM MnCl2 plus 20 mM glycine, enzyme from patient with enzyme deficiency
9.7
L-Pro-L-Met
-
pH 7.8, 37°C, presence of 0.1 mM MnCl2, enzyme from patient with enzyme deficiency
3.2
L-Pro-L-Val
-
pH 7.8, 37°C, presence of 20 mM glycine, enzyme from patient with enzyme deficiency
5.5
L-Pro-L-Val
-
pH 7.8, 37°C, presence of 0.1 mM MnCl2 plus 20 mM glycine, enzyme from patient with enzyme deficiency
10.1
L-Pro-L-Val
-
pH 7.8, 37°C, presence of 0.1 mM MnCl2, enzyme from patient with enzyme deficiency
0.243
L-Val-L-Pro
-
in the presence of 0.1 mM colchicine, 1.0 mM Mn2+, in 30 mM phosphate buffer (pH 7.5) 5.0 mM Ru(bpy)32+, at 37°C
0.269
L-Val-L-Pro
-
in the absence of colchicine, 1.0 mM Mn2+, in 30 mM phosphate buffer (pH 7.5) 5.0 mM Ru(bpy)32+, at 37°C
additional information
additional information
-
kinetics and substrate specificity of wild-type and mutant enzymes, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
10
-
at 30°C, with organophosphorus compound substrate diisopropyl phosphorofluoridate, DFP
additional information
additional information
-
assay method development and evaluation, capillary electrophoresis with Ru(bpy)3 2+ electrochemiluminescence detection, overview
additional information
-
cord blood prolidase activity is 41.4 U/l in term infants and 35.2 U/l in preterm infants
additional information
-
serum prolidase is 952 U/l in patients with pleural tuberculosis
additional information
-
specific activities with melphalan and prodrugs in cancer cell lines, overview
additional information
-
1412 U/l in epithelial ovarian cancer compred to 1338 U/l in controls
additional information
-
45.7 U/l for control group, 53.5 U/l for patients with erectile dysfunction
additional information
-
prolidase activity in correlation to aorta diameter, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.8
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
-
assay at
50
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
from pregenancies with healthy fetusses and those with neural tube defect
-
prolidase activity in blood plasma is about 6% as great as in erythrocytes
-
prolidase activity is increased in ovarian cancer, overview
-
from healthy individuals and from tuberculous pleurisy patients, 19.1fold elevated pleural fluid and serum prolidase enzyme activity in patients with tuberculosis pleurisy compared with non-tuberculosis pleurisy group
-
breast cancer tissue shows high enzyme activity, reduced collagen content and decreased expression of beta1-integrins
-
enzyme from a normal human, a human with prolidase deficiency and her mother
-
from healthy human and from patient with enzyme deficiency. Enzyme activity in normal human erythrocyte is strongly enhanced by Gly, L-Ala, L-Ser with MnCl2 and enhanced by D-Leu and D-Val. L-Val and L-Leu are strong inhibitors. Enzyme activity in a patient with enzyme deficiency is also enhanced by Gly, L-Ala, and L-Ser and by D-Leu and L-Val, L-Leu is inhibitory
-
higher expression of prolidase in tumor cells and particularly in melanoma cells
-
inverse relationship of serum and placental levels of prolidase activity
-
from healthy individuals and from tuberculous pleurisy patients, 19.1fold elevated pleural fluid and serum prolidase enzyme activity in patients with tuberculosis pleurisy compared with non-tuberculosis pleurisy group
-
enzyme activity is increased in patients with nonalcoholic steatohepatitis, NASH, compared to controls
-
inverse relationship of serum and placental levels of prolidase activity
-
serum prolidase enzyme activity is significantly higher in patients with non-alcoholic steatohepatitis than controls
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
-
651194, 652676, 653207, 683061, 683457, 683919, 697476, 700612, 708391, 708527, 708889, 709274, 709651, 710614
additional information
-
subscellular localization in cells natively expressing the enzyme and in cells recombinantly expressing the enzyme
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
misfunctioning causes prolidase deficiency, a recessive connective tissue disorder characterized by severe skin lesions, mental retardation and respiratory tract infections
malfunction
metabolism
physiological function
malfunction
-
decreased serum prolidase activity and increased oxidative stress are correlated in early pregnancy loss, overview
malfunction
-
enzyme activity is increased in aortic dilatation compared to controls
malfunction
-
enzyme activity is increased in patients with nonalcoholic steatohepatitis, NASH, compared to controls, significant correlation between serum prolidase enzyme activity and fibrosis score in patients with NASH
malfunction
-
prolidase activity is significantly increased in patients with thalassemia major compared to the controls, relationship between prolidase activity and oxidative status in patients with thalassemia major, overview
malfunction
-
prolidase deficiency is a rare autosomal recessive disorder that affects the connective tissue. Symptoms of prolidase deficiency include skin lesions, mental retardation and recurrent respiratory infections. Prolidase is linked to collagen metabolism and is associated with melanoma. Prolidase is essential for collagen breakdown and the lack of this enzyme results in serious skin abnormalities. While an increase in prolidase activity and a decrease in collagen in breast cancer tissue may cause increased cancer risk. Recombinant human prolidase is used for enzyme replacement therapy
malfunction
-
prolidase deficiency is a rare, pan-ethnic, autosomal recessive disease with a broad phenotypic spectrum
malfunction
-
serum prolidase activity and oxidative stress are significantly associated with the presence of etal growth restriction, the correlation between serum prolidase activity and markers of oxidative stress are represented as increased serum total oxidative status level and decreased serum total antioxidant capacity and total free sulfhydryl levels, suggesting an association of collagen turnover and oxidative stress in vascular dysfunction, overview
metabolism
-
prolidase catalyzes the final step of collgane breakdown, releasing free proline for collagen recycling
metabolism
-
prolidase plays an important role in collagen metabolism, matrix remodeling and cell growth. Additionally, the final step of collagen degradation in the extracellular matrix is mediated by prolidase
physiological function
-
prolidase activity may be a step-limiting factor in the regulation of collagen biosynthesis
physiological function
-
prolidase is a marker of collagen turnover. The enzyme activity is higher in women with early pregnancy loss than in those without. Collagen turnover is increased in patients with early pregnancy loss and may be an etiopathological factor of this disease
physiological function
-
prolidase is a specific imidodipeptidase involved in collagen degradation
physiological function
-
prolidase plays an important role in collagen metabolism, matrix remodeling and cell growth. Additionally, the final step of collagen degradation in the extracellular matrix is mediated by prolidase
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). PEPD_HUMAN
493
0
54548
Swiss-Prot
other Location (Reliability: 5)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
108000 - 116000
185000
-
gel filtration, prolidase II from normal human and mother of patient with prolidase deficiencyr
53000
-
x * 58000, processed glycoslyated enzyme, SDS-PAGE, x * 53000, unprocessed enzyme, SDS-PAGE
54305
56000
57000
-
2 * 54305, sequence calculation, 2 * 55000-58000, native enzyme from different tissues, 2 * 56000, recombinant enzyme from Saccharomyces cerevisiae, 2 * 73000, recombinant enzyme from Pichia pastoris, 2 * 58000, recombinant enzyme from CHO cells, 2 * 57000, recombinant enzyme from Escherichia coli
58000
73000
108000 - 116000
-
gel filtration, prolidase I from normal human and mother of patient with prolidase deficiency
54305
-
2 * 54305, sequence calculation, 2 * 55000-58000, native enzyme from different tissues, 2 * 56000, recombinant enzyme from Saccharomyces cerevisiae, 2 * 73000, recombinant enzyme from Pichia pastoris, 2 * 58000, recombinant enzyme from CHO cells, 2 * 57000, recombinant enzyme from Escherichia coli
56000
-
2 * 56000, SDS-PAGE, prolidase I from normal human and mother of patient with prolidase deficiencyr
56000
-
2 * 54305, sequence calculation, 2 * 55000-58000, native enzyme from different tissues, 2 * 56000, recombinant enzyme from Saccharomyces cerevisiae, 2 * 73000, recombinant enzyme from Pichia pastoris, 2 * 58000, recombinant enzyme from CHO cells, 2 * 57000, recombinant enzyme from Escherichia coli
58000
-
2 * 58000, homodimerization via leucine zipper motif is required for activity, the active site is not required for dimerization
58000
-
x * 58000, processed glycoslyated enzyme, SDS-PAGE, x * 53000, unprocessed enzyme, SDS-PAGE
58000
-
2 * 54305, sequence calculation, 2 * 55000-58000, native enzyme from different tissues, 2 * 56000, recombinant enzyme from Saccharomyces cerevisiae, 2 * 73000, recombinant enzyme from Pichia pastoris, 2 * 58000, recombinant enzyme from CHO cells, 2 * 57000, recombinant enzyme from Escherichia coli
73000
-
2 * 54305, sequence calculation, 2 * 55000-58000, native enzyme from different tissues, 2 * 56000, recombinant enzyme from Saccharomyces cerevisiae, 2 * 73000, recombinant enzyme from Pichia pastoris, 2 * 58000, recombinant enzyme from CHO cells, 2 * 57000, recombinant enzyme from Escherichia coli
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
structure comparison to the enzyme from Pyrococcus horikoshii OT3 prolidase, overview
dimer
additional information
?
-
x * 58000, processed glycoslyated enzyme, SDS-PAGE, x * 53000, unprocessed enzyme, SDS-PAGE
dimer
-
2 * 56000, SDS-PAGE, prolidase I from normal human and mother of patient with prolidase deficiencyr
dimer
-
2 * 58000, homodimerization via leucine zipper motif is required for activity, the active site is not required for dimerization
dimer
-
2 * 54305, sequence calculation, 2 * 55000-58000, native enzyme from different tissues, 2 * 56000, recombinant enzyme from Saccharomyces cerevisiae, 2 * 73000, recombinant enzyme from Pichia pastoris, 2 * 58000, recombinant enzyme from CHO cells, 2 * 57000, recombinant enzyme from Escherichia coli
additional information
-
crystal structure and active site organization, overview
additional information
-
hydrodynamic properties of wild-type and mutant DPP8s, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
phosphoprotein
proteolytic modification
-
a 29 amino acid signal or propeptide is cleaved from the enzyme after synthesis
glycoprotein
-
5 kDa N-linked glycosyl residue, glycosylation is required for activity
glycoprotein
-
prolidase contains two putative site for N-glycosylation at N13 and N172, and one putative site for O-glycosylation at T458, about 0.5% of carbohydrate content
phosphoprotein
-
enzyme phosphorylation on serine/threonine residue activating the enzyme
phosphoprotein
-
four S109, S134, S198, S236, one T86, and two Y117, Y124 putative sites for phosphorylation, prolidase is both a phosphotyrosine and a phosphothreonine/serine enzyme, both phosphorylations, mediated respectively by Mapk pathway and NO/cGMP signaling, upregulate prolidase activity
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
F822A
-
site-directed mutagenesis, the mutant enzyme shows reduced activity compared to the wild-type enzyme
H859A
-
site-directed mutagenesis, the mutant enzyme shows reduced activity compared to the wild-type enzyme
S202F
V833A
-
site-directed mutagenesis, the mutant enzyme shows reduced activity compared to the wild-type enzyme
Y231del
-
homozygous mutation observed in two unrelated patients with enzyme deficiency. Mutation results in loss of enzyme activity in skin fibroblasts. Long-term cultured fibroblasts bearing the mutant accumulate Gly-L-Pro dipeptide intracellularly
Y256X
-
a homozygous nonsense C > G transition at nucleotide 768 is a naturally occuring mutation, which leads to recalcitrant leg ulceration, splenomegaly, and photosensitive rash due to prolidase deficiency, phenotype, overview
Y844A
-
site-directed mutagenesis, the mutant enzyme shows reduced activity compared to the wild-type enzyme
additional information
additional information
-
construction and expression of leucine zipper mutants and active site mutants, the former show no remaining activity, while the latter are not catalytically active but are still able to dimerize
additional information
-
complete map of the known PEPD mutant alleles causing prolidase deficiency, which is a rare recessive disorder characterized by severe skin lesions, single amino acid substitutions, exon splicing, deletions and a duplication are described as causative for the disease and are mainly located at highly conserved amino acids in the sequence of prolidase, genotype-phenotype correlation, clinical phenotype, overview
additional information
-
enzyme decficiency leads to a rare autosomal recessive disease, characterized by a wide range of clinical outcomes, including severe skin lesions, mental retardation, and infections of the respiratory tract, genotype/phenotype relationship, overview
additional information
-
identification of 17 mutations involved in prolidase deficiency, a rare, pan-ethnic, autosomal recessive disease with a broad phenotypic spectrum. Phenotypes of 20 prolidase deficient patients of Arab Moslem and Druze origin from 10 kindreds residing in northern Israel, overview
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
37°C, purified recombinant enzyme, loss of almost all activity after 2 days, 70% remaining activity after one day for the detagged enzyme, 47% remaining activity for the tagged enzyme
-
37°C, recombinant enzyme from expression in Escherichia coli, stable for 6 days
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged enzyme from Escherichia coli by nickel affinity chromatography, removal of His-tag by factor Xa
-
recombinant His-tagged wild-type and mutant enzymes from HEK-293T cells by nickel affinity and anion exchange chromatography, followed by gel filtration
-
recombinant N-terminally His-tagged enzyme from Escherichia coli by nickel affinity chromatography to homogeneity, on-column digestion of the N-terminal His-tag by factor Xa
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of N-etrminally His-tagged enzyme in Escherichia coli strain BL21
DNA and amino acid sequence analysis, high homology to dipeptidyl-peptidase II, EC 3.4.14.2
-
DNA sequence determination and analysis, expression in human 293T fibroblastic cells as GFP- and Myc-tagged enzymes
-
expression of His-tagged wild-type and mutant enzymes in HEK-293T cells, expression in Spodoptera frugiperda Sf9 cells via baculovirus infection system
-
expression of N-terminally His-tagged enzyme in Escherichia coli strain BL21 (DE3) under the control of the cytomegalovirus promoter and the SP163 enhancer
-
expression of the enzyme, tagged with either HA-tag or Myc-tag, in 293T cells, expressio of mutant enzymes in Escherichia coli XL1-Blue
-
expression of wild-type and mutant enzymes in Escherichia coli, CHO cells, Pichia pastoris, or Saccharomyces cerevisiae, DNA and amino acid sequence determination and anaylsis, recombinant human prolidase expressed in Pichia pastoris catalyzes the hydrolysis of organophosphorus compounds as well as the digestion of Gly-Pro dipeptides
-
gene PEPD, localized on chromosome 19, genetic structure and organization, expression in CHO cells and in colorectal cancer cells
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
drug development
food industry
-
prolidase can be used in dietary industry as bitterness reducing agent
medicine
diagnostics
-
cord blood prolidase activity may be a good indicator of fetal maturation and gestational age
diagnostics
-
prolidase activity may be a useful adjunctive tool in predicting liver fibrosis, especially in the absence of advanced fibrosis and other conditions, which may affect the interpretation of prolidase activity
diagnostics
-
prolidase is a potential biomarker for melanoma, and the enzyme is a target for drug development in cancer therapy
drug development
-
the enzyme is used as target enzyme for specific melanoma prodrug activation
drug development
-
prolidase is a potential biomarker for melanoma, and the enzyme is a target for drug development in cancer therapy
medicine
-
enzyme is a possible target for doxycyclin-induced inhibition of collagen synthesis in the treatment of osteoarthritis
medicine
-
elevated pH-value in vaginal fluid accompanied by high sialidase and high enzyme activity are associated with low and verly low birth weight and early preterm at less than 35 or 32 weeks gestation
medicine
-
enzyme activity in normal human erythrocyte is strongly enhanced by Gly, L-Ala, L-Ser with MnCl2 and enhanced by D-Leu and D-Val. L-Val and L-Leu are strong inhibitors. Enzyme activity in a patient with enzyme deficiency is also enhanced by Gly, L-Ala, and L-Ser and by D-Leu and L-Val, L-Leu is inhibitory
medicine
-
no statistical difference in serum enzyme activity between postmenopausal osteoporotic, postmenopausal nonosteoporotic and premenopausal healthy women. No significant correlations between serum enzyme level and any biomarkers of bone turnover as well as bone mineral density
medicine
-
patients with severe phenotype of enzyme deficiency showing infection, hepatosplenomegaly, thrombocytopenia, classic skin ulcers, and multisystem involvement. Enzyme activity in patients is nearly undetectable due to a single nucleotide mutation c.793 T>C in exon 11, resulting in a premature stop codon at amino acid residue 265
medicine
-
teloid tissue shows up to 4fold increase in enzyme activity compared to normal skin. Elevated enzyme activity is accompanied by increase in concentrations of aminoterminal propeptide of type I procollagen and carboxyterminal telopeptide of type I collagen and increased collagen turnover index
medicine
-
prolidase activity in bronchial asthma and pathogenesis is significant as a collagen turnover indicator and can be used in both to evaluate pathogenesis and prognosis
medicine
-
prolidase-loaded chitosan nanoparticles permit to restore prolidase activity in prolidase deficiency fibroblasts for 8 days
medicine
-
serum prolidase activity is significantly associated with the presence and severity of coronary artery disease, elevated serum prolidase activity may be an independent predictor of coronary atherosclerosis
medicine
-
the presence of atrial fibrillation in patients with severe mitral stenosis may be associated with the plasma prolidase activity
medicine
-
the serum prolidase enzyme activity of patients with steatohepatitis is significantly increased compared with the patients with simple steatosis and controls, serum prolidase enzyme activity is positively correlated with the grade of liver fatty infiltration, lobular inflammation, non-alcoholic fatty liver disease activity score, and stage of fibrosis, serum prolidase enzyme activity is the best predictor for distinguishing steatohepatitis from simple steatosis
medicine
-
Recombinant human prolidase is used for enzyme replacement therapy in prolidase deficiency
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Endo, F.; Tanoue, A.; Nakai, H.; Hata, A.; Indo, Y.; Titani, K.; Matsuda, I.
Primary structure and gene localization of human prolidase
J. Biol. Chem.
264
4476-4481
1989
Homo sapiens
Myara, I.; Moatti, N.; Lemonnier, A.
Separation of two erythrocyte prolidase isoforms by fast protein liquid chromatography; application to prolidase deficiency
J. Chromatogr.
493
170-175
1989
Homo sapiens
Richter, A.M.; Lancaster, G.L.; Choy, F.Y.M.; Hechtman, P.
Purification and characterization of activated human erythrocyte prolidase
Biochem. Cell Biol.
67
34-41
1989
Homo sapiens
Butterworth, J.; Priestman, D.A.
Prolidases of human skin fibroblasts
Biochem. Soc. Trans.
13
237
1985
Homo sapiens
-
Underwood, R.; Chiravuri, M.; Lee, H.; Schmitz, T.; Kabcenell, A.K.; Yardley, K.; Huber, B.T.
Sequence, purification, and cloning of an intracellular serine protease, quiescent cell proline dipeptidase
J. Biol. Chem.
274
34053-34058
1999
Homo sapiens
Myara, I.; Cosson, C.; Moatti, N.; Lemonnier, A.
Human kidney prolidase--purification, preincubation properties and immunological reactivity
Int. J. Biochem.
26
207-214
1994
Homo sapiens
Ohhashi, T.; Ohno, t.; Arata, J.; Sugahara, K.; Kodama, H.
Characterization of prolidase I and II from erythrocytes of a control, a patient with prolidase deficiency and her mother
Clin. Chim. Acta
187
1-10
1990
Homo sapiens
Chiravuri, M.; Schmitz, T.; Yardley, K.; Underwood, R.; Dayal, Y.; Huber, B.T.
A novel apoptotic pathway in quiescent lymphocytes identified by inhibition of a post-proline cleaving aminodipeptidase: a candidate target protease, quiescent cell proline dipeptidase
J. Immunol.
163
3092-3099
1999
Homo sapiens
Masuda, S.; Watanabe, H.; Morioka, M.; Fujita, Y.; Ageta, T.; Kodama, H.
Characteristics of partially purified prolidase and prolinase from the human prostate
Acta Med. Okayama
48
173-179
1994
Homo sapiens
Muszynska, A.; Wolczynski, S.; Palka, J.
The mechanism for anthracycline-induced inhibition of collagen biosynthesis
Eur. J. Pharmacol.
411
17-25
2001
Homo sapiens
Karna, E.; Palka, J.; Wolczynski, S.
Doxycycline-induced inhibition of prolidase activity in human skin fibroblasts and its involvement in impaired collagen biosynthesis
Eur. J. Pharmacol.
430
25-31
2001
Homo sapiens
Araki, H.; Li, Y.; Yamamoto, Y.; Haneda, M.; Nishi, K.; Kikkawa, R.; Ohkubo, I.
Purification, molecular cloning, and immunohistochemical localization of dipeptidyl peptidase II from the rat kidney and its identity with quiescent cell proline dipeptidase
J. Biochem.
129
279-288
2001
Homo sapiens
Chiravuri, M.; Lee, H.; Mathieu, S.L.; Huber, B.T.
Homodimerization via a leucine zipper motif is required for enzymatic activity of quiescent cell proline dipeptidase
J. Biol. Chem.
275
26994-26999
2000
Homo sapiens
Chiravuri, M.; Agarraberes, F.; Mathieu, S.L.; Lee, H.; Huber, B.T.
Vesicular localization and characterization of a novel post-proline-cleaving aminodipeptidase, quiescent cell proline dipeptidase
J. Immunol.
165
5695-5702
2000
Homo sapiens
Surazynski, A.; Palka, J.; Wolczynski, S.
Phosphorylation of prolidase increases the enzyme activity
Mol. Cell. Biochem.
220
95-101
2001
Homo sapiens
Wang, W.; Liu, G.; Yamashita, K.; Manabe, M.; Kodama, H.
Characteristics of prolinase against various iminodipeptides in erythrocyte lysates from a normal human and a patient with prolidase deficiency
Clin. Chem. Lab. Med.
42
1102-1108
2004
Homo sapiens
Wang, S.H.; Liu, M.; Chi, M.G.; Wang, Q.D.; Sun, M.J.
Production of human liver prolidase by Saccharomyces cerevisiae as host cells
Acta Pharmacol. Sin.
25
794-800
2004
Homo sapiens
Wang, H.; Kurien, B.T.; Lundgren, D.; Patel, N.C.; Kaufman, K.M.; Miller, D.L.; Porter, A.C.; DSouza, A.; Nye, L.; Tumbush, J.; Hupertz, V.; Kerr, D.S.; Kurono, S.; Matsumoto, H.; Scofield, R.H.
A nonsense mutation of PEPD in four Amish children with prolidase deficiency
Am. J. Med. Genet. A
140
580-585
2006
Homo sapiens
Cauci, S.; McGregor, J.; Thorsen, P.; Grove, J.; Guaschino, S.
Combination of vaginal pH with vaginal sialidase and prolidase activities for prediction of low birth weight and preterm birth
Am. J. Obstet. Gynecol.
192
489-496
2005
Homo sapiens
Verit, F.F.; Geyikli, I.; Yazgan, P.; Celik, A.
Correlations of serum prolidase activity between bone turnover markers and mineral density in postmenopausal osteoporosis
Arch. Gynecol. Obstet.
274
133-137
2006
Homo sapiens
Wang, S.H.; Zhi, Q.W.; Sun, M.J.
Purification and characterization of recombinant human liver prolidase expressed in Saccharomyces cerevisiae
Arch. Toxicol.
79
253-259
2005
Homo sapiens
Lupi, A.; Rossi, A.; Vaghi, P.; Gallanti, A.; Cetta, G.; Forlino, A.
N-benzyloxycarbonyl-L-proline: An in vitro and in vivo inhibitor of prolidase
Biochim. Biophys. Acta
1744
157-163
2005
Homo sapiens, Mus musculus
Duong, H.S.; Zhang, Q.Z.; Le, A.D.; Kelly, A.P.; Kamdar, R.; Messadi, D.V.
Elevated prolidase activity in keloids: correlation with type I collagen turnover
Br. J. Dermatol.
154
820-828
2006
Homo sapiens
Liu, G.; Nakayama, K.; Sagara, Y.; Awata, S.; Yamashita, K.; Manabe, M.; Kodama, H.
Characterization of prolidase activity in erythrocytes from a patient with prolidase deficiency: comparison with prolidase I and II purified from normal human erythrocytes
Clin. Biochem.
38
625-631
2005
Homo sapiens
Liu, G.; Nakayama, K.; Awata, S.; Wang, W.; Yamashita, K.; Manabe, M.; Kodama, H.
Effects of amino acids and its metabolites on prolidase activity against various iminodipeptides in erythrocytes from normal human and a patient with prolidase deficiency
Clin. Chim. Acta
350
211-217
2004
Homo sapiens
Lupi, A.; De Riso, A.; Torre, S.D.; Rossi, A.; Campari, E.; Vilarinho, L.; Cetta, G.; Forlino, A.
Characterization of a new PEPD allele causing prolidase deficiency in two unrelated patients: natural-occurrent mutations as a tool to investigate structure-function relationship
J. Hum. Genet.
49
500-506
2004
Homo sapiens
Surazynski, A.; Sienkiewicz, P.; Wolczynski, S.; Palka, J.
Differential effects of echistatin and thrombin on collagen production and prolidase activity in human dermal fibroblasts and their possible implication in beta1-integrin-mediated signaling
Pharm. Res.
51
217-221
2005
Homo sapiens
Wang, S.H.; Zhi, Q.W.; Sun, M.J.
Dual activities of human prolidase
Toxicol. In Vitro
20
71-77
2006
Homo sapiens
Uramatsu, M.; Liu, G.; Uramatsu, S.; Zhang, M.; Wang, W.; Nakayama, K.; Manabe, M.; Kodama, H.
Different effects of sulfur amino acids on prolidase and prolinase activity in normal and prolidase-deficient human erythrocytes
Clin. Chim. Acta
375
129-135
2007
Homo sapiens
Lee, H.J.; Chen, Y.S.; Chou, C.Y.; Chien, C.H.; Lin, C.H.; Chang, G.G.; Chen, X.
Investigation of the dimer interface and substrate specificity of prolyl dipeptidase DPP8
J. Biol. Chem.
281
38653-38662
2006
Homo sapiens
Lupi, A.; Tenni, R.; Rossi, A.; Cetta, G.; Forlino, A.
Human prolidase and prolidase deficiency: an overview on the characterization of the enzyme involved in proline recycling and on the effects of its mutations
Amino Acids
35
739-752
2008
Homo sapiens, Pyrococcus furiosus
Son, E.D.; Choi, G.H.; Kim, H.; Lee, B.; Chang, I.S.; Hwang, J.S.
Alpha-ketoglutarate stimulates procollagen production in cultured human dermal fibroblasts, and decreases UVB-induced wrinkle formation following topical application on the dorsal skin of hairless mice
Biol. Pharm. Bull.
30
1395-1399
2007
Homo sapiens
Buszman, E.; Wrzesniok, D.; Surazynski, A.; Patka, J.; Moleda, K.
Effect of melanin on netilmicin-induced inhibition of collagen biosynthesis in human skin fibroblasts
Bioorg. Med. Chem.
14
8155-8161
2006
Homo sapiens
Ipcioglu, O.M.; Ozcan, O.; Gultepe, M.; Deniz, O.; Akgul, E.O.
Prolidase activity in serum and pleural fluids in patients with tuberculous pleural effussion
Clin. Biochem.
41
670-675
2008
Homo sapiens
Yuan, J.; Wei, H.; Jin, W.; Yang, X.; Wang, E.
Kinetic study of paracetamol on prolidase activity in erythrocytes by capillary electrophoresis with Ru(bpy)3 2+ electrochemiluminescence detection
Electrophoresis
27
4047-4051
2006
Homo sapiens
Lupi, A.; Della Torre, S.; Campari, E.; Tenni, R.; Cetta, G.; Rossi, A.; Forlino, A.
Human recombinant prolidase from eukaryotic and prokaryotic sources. Expression, purification, characterization and long-term stability studies
FEBS J.
273
5466-5478
2006
Homo sapiens
Cechowska-Pasko, M.; Palka, J.; Wojtukiewicz, M.Z.
Enhanced prolidase activity and decreased collagen content in breast cancer tissue
Int. J. Exp. Pathol.
87
289-296
2006
Homo sapiens
Galicka, A.; Nazaruk, J.
Stimulation of collagen biosynthesis by flavonoid glycosides in skin fibroblasts of osteogenesis imperfecta type I and the potential mechanism of their action
Int. J. Mol. Med.
20
889-895
2007
Homo sapiens
Miltyk, W.; Karna, E.; Palka, J.A.
Prolidase-independent mechanism of camptothecin-induced inhibition of collagen biosynthesis in cultured human skin fibroblasts
J. Biochem.
141
287-292
2007
Homo sapiens
Karna, E.; Miltyk, W.; Surazynski, A.; Patka, J.A.
Protective effect of hyaluronic acid on interleukin-1-induced deregulation of beta1-integrin and insulin-like growth factor-I receptor signaling and collagen biosynthesis in cultured human chondrocytes
Mol. Cell. Biochem.
308
57-64
2008
Homo sapiens
Citak Kurt, A.N.; Ustundag, B.; Akarsu, S.; Kurt, A.; Yilmaz, E.; Ocal, C.; Aygun, A.D.
Cord blood prolidase activity correlates with gestational age and birth weight
Neonatology
94
110-112
2008
Homo sapiens
Mittal, S.; Song, X.; Vig, B.S.; Amidon, G.L.
Proline prodrug of melphalan targeted to prolidase, a prodrug activating enzyme overexpressed in melanoma
Pharm. Res.
24
1290-1298
2007
Homo sapiens, Sus scrofa
Uramatsu, S.; Liu, G.; Yang, Q.; Uramatsu, M.; Chi, H.; Lu, J.; Yamashita, K.; Kodama, H.
Characterization of prolidase I and II purified from normal human erythrocytes: comparison with prolidase in erythrocytes from a patient with prolidase deficiency
Amino Acids
37
543-551
2009
Homo sapiens
Rabus, M.; Demirbag, R.; Yildiz, A.; Tezcan, O.; Yilmaz, R.; Ocak, A.R.; Alp, M.; Erel, O.; Aksoy, N.; Yakut, C.
Association of prolidase activity, oxidative parameters, and presence of atrial fibrillation in patients with mitral stenosis
Arch. Med. Res.
39
519-524
2008
Homo sapiens
Dunn, R.; Dolianitis, C.
Prolidase deficiency: the use of topical proline for treatment of leg ulcers
Australas. J. Dermatol.
49
237-238
2008
Homo sapiens
Yildiz, A.; Demirbag, R.; Yilmaz, R.; Gur, M.; Altiparmak, I.H.; Akyol, S.; Aksoy, N.; Ocak, A.R.; Erel, O.
The association of serum prolidase activity with the presence and severity of coronary artery disease
Coron. Artery Dis.
19
319-325
2008
Homo sapiens
Kayadibi, H.; Gueltepe, M.; Yasar, B.; Ince, A.T.; Ozcan, O.; Ipcioglu, O.M.; Kurdas, O.O.; Bolat, B.; Benek, Y.Z.; Guveli, H.; Atalay, S.; Ozkara, S.; Keskin, O.
Diagnostic value of serum prolidase enzyme activity to predict the liver histological lesions in non-alcoholic fatty liver disease: A surrogate marker to distinguish steatohepatitis from simple steatosis
Digest. Dis. Sci.
54
1764-1771
2008
Homo sapiens
Colonna, C.; Conti, B.; Perugini, P.; Pavanetto, F.; Modena, T.; Dorati, R.; Iadarola, P.; Genta, I.
Ex vivo evaluation of prolidase loaded chitosan nanoparticles for the enzyme replacement therapy
Eur. J. Pharm. Biopharm.
70
58-65
2008
Homo sapiens
Zhou, L.; Yuan, J.; Yin, J.; Wang, E.
Kinetic study of prolidase activity in erythrocytes against different substrates using capillary electrophoresis with electrochemiluminescence detection
J. Chromatogr. A
1200
255-259
2008
Homo sapiens
Cakmak, A.; Zeyrek, D.; Atas, A.; Celik, H.; Aksoy, N.; Erel, O.
Serum prolidase activity and oxidative status in patients with bronchial asthma
J. Clin. Lab. Anal.
23
132-138
2009
Homo sapiens
Bielawski, K.; Bielawska, A.; S?odownik, T.; Bo?kun-Skornicka, U.; Muszy?ska, A.
Proline-linked nitrosoureas as prolidase-convertible prodrugs in human breast cancer cells
Pharmacol. Rep.
60
171-182
2008
Homo sapiens, Sus scrofa
Theriot, C.M.; Tove, S.R.; Grunden, A.M.
Biotechnological applications of recombinant microbial prolidases
Adv. Appl. Microbiol.
68
99-132
2009
Alteromonas sp., Alteromonas sp. JD6.5, Cavia porcellus, Homo sapiens, Lacticaseibacillus casei, Lacticaseibacillus casei IFPL 731, Lactobacillus delbrueckii, Lactococcus lactis, Pyrococcus furiosus, Stenotrophomonas maltophilia
Falik-Zaccai, T.; Khayat, M.; Luder, A.; Frenkel, P.; Magen, D.; Brik, R.; Gershoni-Baruch, R.; Mandel, H.
A broad spectrum of developmental delay in a large cohort of prolidase deficiency patients demonstrates marked interfamilial and intrafamilial phenotypic variability
Am. J. Med. Genet. B Neuropsychiatr. Genet.
153
46-56
2010
Homo sapiens
Vural, M.; Toy, H.; Camuzcuoglu, H.; Aksoy, N.
Comparison of prolidase enzyme activities of maternal serum and placental tissue in patients with early pregnancy failure
Arch. Gynecol. Obstet.
283
953-958
2011
Homo sapiens
Besio, R.; Alleva, S.; Forlino, A.; Lupi, A.; Meneghini, C.; Minicozzi, V.; Profumo, A.; Stellato, F.; Tenni, R.; Morante, S.
Identifying the structure of the active sites of human recombinant prolidase
Eur. Biophys. J.
39
935-945
2010
Homo sapiens (P12955), Homo sapiens
Camuzcuoglu, H.; Arioz, D.T.; Toy, H.; Kurt, S.; Celik, H.; Aksoy, N.
Assessment of preoperative serum prolidase activity in epithelial ovarian cancer
Eur. J. Obstet. Gynecol. Reprod. Biol.
147
97-100
2009
Homo sapiens
Klar, A.; Navon-Elkan, P.; Rubinow, A.; Branski, D.; Hurvitz, H.; Christensen, E.; Khayat, M.; Falik-Zaccai, T.C.
Prolidase deficiency: it looks like systemic lupus erythematosus but it is not
Eur. J. Pediatr.
169
727-732
2010
Homo sapiens
Vural, M.; Camuzcuoglu, H.; Toy, H.; Aksoy, N.
Amniotic fluid prolidase activity and oxidative status in neural tube defects
Fetal. Diagn. Ther.
28
34-39
2010
Homo sapiens
Toy, H.; Camuzcuoglu, H.; Camuzcuoglu, A.; Celik, H.; Aksoy, N.
Decreased serum prolidase activity and increased oxidative stress in early pregnancy loss
Gynecol. Obstet. Invest.
69
122-127
2010
Homo sapiens
Savas, M.; Yeni, E.; Celik, H.; Ciftci, H.; Utangac, M.; Oncel, H.; Altunkol, A.; Verit, A.
The association of serum prolidase activity and erectile dysfunction
J. Androl.
31
146-154
2010
Homo sapiens
Horoz, M.; Aslan, M.; Bolukbas, F.F.; Bolukbas, C.; Nazligul, Y.; Celik, H.; Aksoy, N.
Serum prolidase enzyme activity and its relation to histopathological findings in patients with non-alcoholic steatohepatitis
J. Clin. Lab. Anal.
24
207-211
2010
Homo sapiens
Cakmak, A.; Soker, M.; Koc, A.; Aksoy, N.
Prolidase activity and oxidative status in patients with thalassemia major
J. Clin. Lab. Anal.
24
6-11
2010
Homo sapiens
Toy, H.; Camuzcuoglu, H.; Arioz, D.T.; Kurt, S.; Celik, H.; Aksoy, N.
Serum prolidase activity and oxidative stress markers in pregnancies with intrauterine growth restricted infants
J. Obstet. Gynaecol. Res.
35
1047-1053
2009
Homo sapiens
Karna, E.; Szoka, L.; Palka, J.A.
Betulinic acid inhibits the expression of hypoxia-inducible factor 1alpha and vascular endothelial growth factor in human endometrial adenocarcinoma cells
Mol. Cell. Biochem.
340
15-20
2010
Homo sapiens
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