Information on EC 3.4.13.9 - Xaa-Pro dipeptidase

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

EC NUMBER
COMMENTARY hide
3.4.13.9
-
RECOMMENDED NAME
GeneOntology No.
Xaa-Pro dipeptidase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
hydrolysis of Xaa-/-Pro dipeptides; also acts on aminoacyl-hydroxyamine analogues. No action on Pro-Pro
show the reaction diagram
hydrolysis of Xaa-/-Pro dipeptides; also acts on aminoacyl-hydroxyproline analogs. No action on Pro-Pro
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
dipeptide hydrolase
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CAS REGISTRY NUMBER
COMMENTARY hide
9025-32-5
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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Automatic Mining of ENzyme DAta
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Automatic Mining of ENzyme DAta
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Manually annotated by BRENDA team
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Automatic Mining of ENzyme DAta
random source, mixed breed dogs, gene pepQ
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Manually annotated by BRENDA team
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Automatic Mining of ENzyme DAta
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Automatic Mining of ENzyme DAta
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Automatic Mining of ENzyme DAta
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Manually annotated by BRENDA team
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Automatic Mining of ENzyme DAta
Lactococcus lactis NRRL B-1821
gene pepQ; strain NRRL B-1821, gene pepQ
SwissProt
Manually annotated by BRENDA team
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Automatic Mining of ENzyme DAta
monkey
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Manually annotated by BRENDA team
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Automatic Mining of ENzyme DAta
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Automatic Mining of ENzyme DAta
Oenococcus oeni is the principal microorganism responsible for the malolactic fermentation, which decreases total acidity and improves the quality and stability of wine, strain IOEB 8413, gene pepQ
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Manually annotated by BRENDA team
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Automatic Mining of ENzyme DAta
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Automatic Mining of ENzyme DAta
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Automatic Mining of ENzyme DAta
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Automatic Mining of ENzyme DAta
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UniProt
Manually annotated by BRENDA team
salamander
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Automatic Mining of ENzyme DAta
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Automatic Mining of ENzyme DAta
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Automatic Mining of ENzyme DAta
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Automatic Mining of ENzyme DAta
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Automatic Mining of ENzyme DAta
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Automatic Mining of ENzyme DAta
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Automatic Mining of ENzyme DAta
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UniProt
Manually annotated by BRENDA team
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UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
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
4-nitrophenyl soman + H2O
?
show the reaction diagram
-
-
-
-
?
Ala-Ala + H2O
Ala + Ala
show the reaction diagram
-
-
-
-
?
Ala-Phe + H2O
Ala + Phe
show the reaction diagram
-
-
-
-
?
Ala-Pro + H2O
Ala + Pro
show the reaction diagram
Ala-Pro-amino-4-trifluoromethylcoumarin + H2O
?
show the reaction diagram
-
-
-
?
Ala-Pro-amino-4-trifluoromethylcoumarin + H2O
alanine + Pro-4-trifluoromethylcoumarin
show the reaction diagram
Ala-Pro-Gly + H2O
Ala + Pro-Gly
show the reaction diagram
-
-
-
?
Arg-Pro + H2O
Arg + Pro
show the reaction diagram
Asp-Pro + H2O
Asp + Pro
show the reaction diagram
-
-
-
-
?
Gly-Hyp + H2O
Gly + Hyp
show the reaction diagram
Gly-L-Pro + H2O
Gly + L-Pro
show the reaction diagram
Gly-Pro
?
show the reaction diagram
-
-
-
-
-
Gly-Pro + H2O
Gly + Pro
show the reaction diagram
Gly-Pro + H2O
Glycine + proline
show the reaction diagram
-
-
-
?
Gly-Pro-4-trifluoromethylcoumarin-7-amide + H2O
Gly + Pro + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
-
-
-
-
?
Gly-Pro-Ala + H2O
Gly + Pro-Ala
show the reaction diagram
-
-
-
?
Gly-Pro-Gly + H2O
Gly + Pro-Gly
show the reaction diagram
-
-
-
?
Gly-Pro-p-nitroanilide + H2O
Gly + Pro + p-nitroaniline
show the reaction diagram
-
-
-
-
?
glycyl-L-hydroxyproline + H2O
Gly + L-hydroxyproline
show the reaction diagram
His-Pro + H2O
His + Pro
show the reaction diagram
Ile-Pro + H2O
Ile + Pro
show the reaction diagram
L-Ala-Pro + H2O
L-Ala + Pro
show the reaction diagram
L-Arg-L-Pro + H2O
L-Arg + L-Pro
show the reaction diagram
-
12.0% activity compared to L-Leu-L-Pro, in the presence of 1 mM ZnCl2
-
-
?
L-Leu-L-Pro + H2O
L-Leu + L-Pro
show the reaction diagram
L-Lys-L-Pro + H2O
L-Lys + L-Pro
show the reaction diagram
-
6.6% activity compared to L-Leu-L-Pro, in the presence of 1 mM ZnCl2
-
-
?
L-Met-L-Pro
L-Met + L-Pro
show the reaction diagram
-
-
-
-
?
L-Met-L-Pro + H2O
L-Met + L-Pro
show the reaction diagram
L-Met-Pro + H2O
L-Met + Pro
show the reaction diagram
-
-
-
-
?
L-Phe-L-Pro + H2O
L-Phe + L-Pro
show the reaction diagram
-
23.8% activity compared to L-Leu-L-Pro, in the presence of 1 mM ZnCl2
-
-
?
L-Phe-Pro + H2O
L-Phe + Pro
show the reaction diagram
L-Pro-Gly + H2O
L-Pro + Gly
show the reaction diagram
-
-
-
-
?
L-Pro-L-Ala + H2O
L-Pro + L-Ala
show the reaction diagram
-
-
-
-
?
L-Pro-L-Asp + H2O
L-Pro + L-Asp
show the reaction diagram
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-
-
-
?
L-Pro-L-Glu + H2O
L-Pro + L-Glu
show the reaction diagram
-
-
-
-
?
L-Pro-L-Leu + H2O
L-Pro + L-Leu
show the reaction diagram
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-
-
-
?
L-Pro-L-Met + H2O
L-Pro + L-Met
show the reaction diagram
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-
-
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?
L-Pro-L-Phe + H2O
L-Pro + L-Phe
show the reaction diagram
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-
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?
L-Pro-L-Ser + H2O
L-Pro + L-Ser
show the reaction diagram
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-
-
-
?
L-Pro-L-Val + H2O
L-Pro + L-Val
show the reaction diagram
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-
-
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?
L-Val-L-Pro + H2O
L-Val + L-Pro
show the reaction diagram
L-Val-Pro + H2O
L-Val + Pro
show the reaction diagram
Leu-Pro + H2O
Leu + Pro
show the reaction diagram
Lys-Pro + H2O
Lys + Pro
show the reaction diagram
melphalan + H2O
?
show the reaction diagram
Met-Pro + H2O
L-Met + L-Pro
show the reaction diagram
-
68% of the activity with Gly-L-Pro
-
-
?
Met-Pro + H2O
Met + Pro
show the reaction diagram
Phe-Pro + H2O
Phe + Pro
show the reaction diagram
Pro-Ala + H2O
Pro + Ala
show the reaction diagram
Pro-Hyp + H2O
Pro + Hyp
show the reaction diagram
Pro-Pro + H2O
Pro + Pro
show the reaction diagram
prophalan-D + H2O
?
show the reaction diagram
prophalan-L + H2O
?
show the reaction diagram
Ser-Pro + H2O
Ser + Pro
show the reaction diagram
soman + H2O
?
show the reaction diagram
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organophosphorus acid anhydrolase activity
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-
?
Thr-Pro + H2O
Thr + Pro
show the reaction diagram
Tyr-Pro + H2O
Tyr + Pro
show the reaction diagram
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-
-
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?
Val-Pro + H2O
Val + Pro
show the reaction diagram
Xaa-Pro + H2O
Xaa + Pro
show the reaction diagram
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-
?
additional information
?
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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
Gly-Pro
?
show the reaction diagram
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Gly-Pro + H2O
Glycine + proline
show the reaction diagram
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-
?
melphalan + H2O
?
show the reaction diagram
-
prolidase-dependence of prodrug cytotoxicity in the cell lines compared to that of the parent drug, melphalan, overview
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?
prophalan-D + H2O
?
show the reaction diagram
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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
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?
prophalan-L + H2O
?
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Cobalt
-
2 atoms per subunit are required for optimum activity
Cu2+
activates; activates
Fe3+
-
stimulation
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
Ni2+
activates; activates
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2S,3R)-3-amino-2-hydroxy-5-methyl-hexanoyl-proline
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(2S,3R)-3-amino-2-hydroxy-5-methylhexanoyl-proline
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1,10-phenanthroline
1,2-Cylcopentanedicarboxylic acid
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2-mercaptoethanol
acetic acid
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inhibts the enzyme in colonic tissue, but not in plasma
betulinic acid
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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
captopril
-
inhibits isozyme PD I dose-dependently, but shows no inhibition of isozyme PD II at 0.1 mM
carmustine
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Colchicine
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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
Cupferron
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N-Hydroxy-N-nitrosobenzeneamine ammonium salt
D,L-4-Amino-4-phosphonobutyrate
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D,L-homocysteine
-
inhibits the activity at 50 mM
D,L-homocysteine-thiolactone
-
inhibits the activities of isozymes prolidase I and II in a concentration-dependent manner
daunorubicin
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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
dithiothreitol
DL-Ethionine
-
activates at concentrations of 1-50 mM, overview
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
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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
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Gly-PSI[CO-CH]-Pro
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iodoacetamide
-
-
iodoacetate
L-isoleucine
-
inhibitory to enzyme isoform prolidase I, activating isoform prolidase II
L-Leu-L-Pro
-
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L-leucine
-
inhibitory to enzyme isoform prolidase I, activating isoform prolidase II
L-proline
-
competitive
L-valine
-
inhibitory to enzyme isoform prolidase I, activating isoform prolidase II
L-valinyl-D-boroproline
-
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melanin
-
30% inhibition at 0.1 mg/ml, reverses inhibition of prolidase by netilmicin
N,N'-diisopropyldiamidofluorophosphate
-
i.e. DDFP or mipafox
N-acetylproline
-
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N-Benzyloxycarbonyl-L-proline
N-[N'-(2-bromoethyl)-N'-nitrosocarbamoyl]-L-proline
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netilmicin
-
80% inhibition at 0.01 mM, reversible by melanin
NiCl2
p-chloromercuribenzoate
p-hydroxymercuribenzoate
paracetamol
-
mechanism of PLD inhibition by paracetamol is noncompetitive inhibition
Phenacetin
-
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phenylacetyl-thioproline
-
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phosphoenolpyruvate
-
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Phosphonates
-
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Phosphonocarboxylates
-
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sodium salicylate
-
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trans-1,2-cyclopentanedicarboxylate
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Z-Pro
-
roughly 80% inhibition at 2.53 mM
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
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
8-Br-cGMP
-
strong and rapid stimulation of enzyme activity by phosphorylation
Acetylsalicylic acid
-
-
alpha-ketoglutarate
-
30% activation at 0.01 mM
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
D,L-homocysteine
-
enhances the activity of isozyme prolidase I at low concentration; weakly enhances the activity of isozyme prolidase II
D,L-methionine
-
slightly enhances the activity of isozyme prolidase I at low concentration; the activity of isozyme prolidase II against L-Met-L-Pro is enhanced by D,L-methionine
D-alanine
-
activation of isoforms prolidase I and prolidase II
D-Ethionine
-
enhances the activity of isozymes prolidase I and II
D-isoleucine
-
activation of isoforms prolidase I and prolidase II
D-Leucine
-
activation of isoforms prolidase I and prolidase II
D-methionine
-
the activity of isozyme prolidase I against Gly-L-Pro is strongly enhanced by D-methionine; the activity of isozyme prolidase II against L-Met-L-Pro is enhanced by D-methionine
D-serine
-
activation of isoforms prolidase I and prolidase II
D-valine
-
activation of isoforms prolidase I and prolidase II
diethyldithiocarbamate
-
activation
glycine
L-alanine
-
activation of isoforms prolidase I and prolidase II
L-ethionine
-
enhances the activity of isozyme prolidase I
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-methionine
-
slightly enhances the activity of isozyme prolidase I at low concentration; the activity of isozyme prolidase II against L-Met-L-Pro is enhanced by L-methionine
L-serine
-
activation of isoforms prolidase I and 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
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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
-
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
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.127 - 8.3
Ala-Pro
6.7
Gly-Hyp
-
-
1.64 - 6.23
Gly-L-Pro
0.006 - 7.1
Gly-Pro
0.39
His-Pro
-
-
0.395 - 23.3
L-Leu-L-Pro
4.11 - 9.89
L-Met-L-Pro
6.8 - 26.9
L-Pro-Gly
4.2 - 19.1
L-Pro-L-Met
3.2 - 28.6
L-Pro-L-Val
0.243 - 0.269
L-Val-L-Pro
0.2 - 10.4
Leu-Pro
0.81 - 14.5
Met-Pro
0.76 - 25
Phe-Pro
12.5
Pro-Hyp
-
-
0.38
Pro-Pro
-
-
0.06 - 4.2
Val-Pro
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.2 - 22
Ala-Pro
683
Gly-Pro
Homo sapiens
-
-
55.3
Ile-Pro
Cavia porcellus
-
-
109
L-Met-L-Pro
Escherichia coli
-
-
111 - 2861
Leu-Pro
115 - 7481
Met-Pro
additional information
additional information
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
980 - 2049
Leu-Pro
2995
13 - 2006
Met-Pro
1169
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
15.3
L-Leu-L-Pro
-
wild type enzyme, in 20 mM sodium citrate (pH 6.5), and 1 mM ZnCl2, at 50C
additional information
additional information
-
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.05
captopril
Rattus norvegicus
-
isozyme PD I, pH 7.8, 37C
0.038
carmustine
Sus scrofa
-
in 0.05 M Tris-HCl, pH 7.8, 2 mM MnCl2, at 37C
0.005
N-Benzyloxycarbonyl-L-proline
Rattus norvegicus
-
isozyme PD I, pH 7.8, 37C
0.082
N-[N'-(2-bromoethyl)-N'-nitrosocarbamoyl]-L-proline
Sus scrofa
-
in 0.05 M Tris-HCl, pH 7.8, 2 mM MnCl2, at 37C
0.005
netilmicin
Homo sapiens
-
-
0.05
Ni2+
Rattus norvegicus
-
isozyme PD II, pH 7.8, 37C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00000059
-
substrate prophalan-L
0.024
-
PepX, cell extract
0.041
-
PepQ, cell extract
0.129
-
PepI, cell extract