Information on EC 3.4.13.18 - cytosol nonspecific dipeptidase

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

EC NUMBER
COMMENTARY hide
3.4.13.18
-
RECOMMENDED NAME
GeneOntology No.
cytosol nonspecific dipeptidase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
hydrolysis of dipeptides, preferentially hydrophobic dipeptides including prolyl amino acids
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Arginine and proline metabolism
-
-
beta-Alanine metabolism
-
-
gamma-glutamyl cycle
-
-
glutathione degradation (DUG pathway - yeast)
-
-
Histidine metabolism
-
-
Metabolic pathways
-
-
muropeptide degradation
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
9025-31-4
-
9032-23-9
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
Ala-Ala + H2O
Ala + Ala
show the reaction diagram
Ala-Ala-p-nitroanilide + H2O
Ala-Ala + p-nitroaniline
show the reaction diagram
-
-
-
?
Ala-Ile + H2O
Ala + Ile
show the reaction diagram
Ala-Leu + H2O
Ala + Leu
show the reaction diagram
Ala-Pro-p-nitroanilide + H2O
Ala-Pro + p-nitroaniline
show the reaction diagram
Arg-Pro-p-nitroanilide + H2O
Arg-Pro + p-nitroaniline
show the reaction diagram
Asp-Pro-p-nitroanilide + H2O
Asp-Pro + p-nitroaniline
show the reaction diagram
beta-Ala-L-His + H2O
beta-Ala + L-His
show the reaction diagram
carnosine + H2O
?
show the reaction diagram
Gly-Gly + H2O
Gly + Gly
show the reaction diagram
Gly-His + H2O
Gly + His
show the reaction diagram
-
-
-
?
Gly-Ile + H2O
Gly + Ile
show the reaction diagram
Gly-Leu + H2O
Gly + Leu
show the reaction diagram
Gly-Phe + H2O
Gly + Phe
show the reaction diagram
Gly-Pro-p-nitroanilide + H2O
Gly-Pro + p-nitroaniline
show the reaction diagram
Gly-Tyr + H2O
Gly + Tyr
show the reaction diagram
-
-
-
?
Gly-Val + H2O
Gly + Val
show the reaction diagram
His-Ala + H2O
His + Ala
show the reaction diagram
-
-
-
?
Hyp-Gly + H2O
Hyp + Gly
show the reaction diagram
-
-
-
?
L-Ala-4-methylcoumarin 7-amide + H2O
L-Ala + 7-amino-4-methylcoumarin
show the reaction diagram
L-Ala-Gly + H2O
L-Ala + Gly
show the reaction diagram
L-Ala-L-Ser + H2O
L-Ala + L-Ser
show the reaction diagram
-
-
-
-
L-Lys-4-methylcoumarin 7-amide + H2O
L-Lys + 7-amino-4-methylcoumarin
show the reaction diagram
Leu-Arg + H2O
Leu + Arg
show the reaction diagram
-
-
-
?
Leu-Gly + H2O
Leu + Gly
show the reaction diagram
Leu-Leu + H2O
Leu + Leu
show the reaction diagram
Leu-Leu-Leu + H2O
?
show the reaction diagram
-
-
-
-
?
Leu-Pro-p-nitroanilide + H2O
Leu-Pro + p-nitroaniline
show the reaction diagram
-
-
-
-
?
Leu-Ser + H2O
Leu + Ser
show the reaction diagram
-
-
-
?
Lys-Pro-p-nitroanilide + H2O
Lys-Pro + p-nitroaniline
show the reaction diagram
-
-
-
-
?
Met-Ala + H2O
Met + Ala
show the reaction diagram
Met-Glu + H2O
Met + Glu
show the reaction diagram
-
-
-
?
Met-Gly + H2O
Met + Gly
show the reaction diagram
-
-
-
?
Met-Leu + H2O
Met + Leu
show the reaction diagram
Met-Phe + H2O
Met + Phe
show the reaction diagram
-
-
-
?
Met-Pro-p-nitroanilide + H2O
Met-Pro + p-nitroaniline
show the reaction diagram
-
-
-
-
?
N-(3,5-dicarboxy-4-methyl-2-pyrrolcarbonyl)glycine + H2O
?
show the reaction diagram
-
-
-
-
?
Phe-Gly + H2O
Phe + Gly
show the reaction diagram
Phe-Leu + H2O
Phe + Leu
show the reaction diagram
-
-
-
?
Phe-Met + H2O
Phe + Met
show the reaction diagram
-
-
-
?
Pro-Ala + H2O
Pro + Ala
show the reaction diagram
Pro-Asp + H2O
Pro + Asp
show the reaction diagram
-
-
-
-
?
Pro-Glu + H2O
Pro + Glu
show the reaction diagram
-
-
-
-
?
Pro-Gly + H2O
Pro + Gly
show the reaction diagram
Pro-Ile + H2O
Pro + Ile
show the reaction diagram
-
-
-
?
Pro-Leu + H2O
Pro + Leu
show the reaction diagram
Pro-Leu-NH2 + H2O
Pro + Leu-NH2
show the reaction diagram
-
-
-
?
Pro-Lys + H2O
Pro + Lys
show the reaction diagram
-
-
-
?
Pro-Met + H2O
Met + Gly
show the reaction diagram
-
-
-
-
?
Pro-Met + H2O
Pro + Met
show the reaction diagram
Pro-Phe + H2O
Pro + Phe
show the reaction diagram
Pro-Pro + H2O
Pro + Pro
show the reaction diagram
-
-
-
?
Pro-Ser + H2O
Pro + Ser
show the reaction diagram
-
-
-
-
?
Pro-Val + H2O
Pro + Val
show the reaction diagram
Ser-Phe + H2O
Ser + Phe
show the reaction diagram
-
-
-
?
Ser-Pro-p-nitroanilide + H2O
Ser-Pro + p-nitroaniline
show the reaction diagram
-
-
-
-
?
Thr-Leu + H2O
Thr + Leu
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
additional information
?
-
-
DPP8-v3 may play a key role in the immunoregulation of testes and accordingly may influence spermatogenesis and male fertility
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
-
favors the activity towards the substrates Leu-Gly and Ala-Gly
Ni2+
about 75% of the activation with Co2+
additional information
no activation by Cd2+, Zn2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(1S)-1-cyclohexyl-2-(1,3-dihydro-2H-isoindol-2-yl)-2-oxoethanamine
-
IC50: 24 nM
(1S)-1-cyclohexyl-2-(3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethanamine
-
IC50: 3016 nM
(1S)-1-cyclohexyl-2-oxo-2-piperidin-1-ylethanamine
-
IC50: 1448 nM
(1S)-1-cyclohexyl-2-oxo-2-pyrrolidin-1-ylethanamine
-
IC50: 78 nM
(2S)-1-[(2S)-2-amino-4-(3,4-dihydroisoquinolin-2(1H)-yl)-4-oxobutanoyl]pyrrolidine-2-carbonitrile
-
IC50: 19 nM
(2S)-1-[(2S)-2-amino-4-(4-[bis(4-fluorophenyl)methyl]piperazin-1-yl)-4-oxobutanoyl]pyrrolidine-2-carbonitrile
-
IC50: 16 nM
(2S)-2-amino-2-cyclohexyl-1-[(2R)-2-(iminomethyl)cyclopentyl]ethanone
-
IC50: 27 nM
(2S,3S)-3-methyl-1-oxo-1-(1,3-thiazolidin-3-yl)pentan-2-amine
-
IC50: 364 nM
1,10-phenanthroline
1-(1,3-dihydro-2H-isoindol-2-yl)-4-(3,4-dihydroisoquinolin-2(1H)-yl)-1,4-dioxobutan-2-amine
-
IC50: 555 nM
1-(1,3-dihydro-2H-isoindol-2-yl)-4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-1,4-dioxobutan-2-amine
-
IC50: 150 nM
2-mercaptoethanol
4-(4-[bis(4-fluorophenyl)methyl]piperazin-1-yl)-1-(1,3-dihydro-2H-isoindol-2-yl)-1,4-dioxobutan-2-amine
-
IC50: 14 nM
6-([2-({2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl}amino)ethyl]amino)nicotinonitrile
-
IC50: 4574 nM
amastatin
-
-
bestatin
-
-
Carnosinase substrates
-
-
-
Cd2+
-
-
CdCl2
-
-
Cu2+
-
-
cysteine
D-Forms of dipeptides
D-Leu-Gly
DL-homocysteine
-
strong inhibition at 10 and 50 mM, in the presence of 0.1 mM MnCl2
DL-methionine
-
strong inhibition at 10 and 50 mM, in the presence of 0.1 mM MnCl2
ethanol
-
-
Gly-Leu
-
competitive inhibitor of L-Ala-Gly hydrolysis
iodoacetamide
-
-
iodoacetate
Iodosobenzoate
L-alanine
-
poor competitive inhibitor of Ala-Gly hydrolysis
L-leucine
-
strong inhibition of prolinase activity against Pro-Gly regardless wether MnCl2 is present or not
L-methionine
-
inhibition at 10 and 50 mM, in the presence of 0.1 mM MnCl2
L-Val
-
strong inhibition of prolinase activity against Pro-Gly regardless wether MnCl2 is present or not
leucine
-
-
Mg2+
-
slight inhibition
N-(2-pyrrolcarbonyl)glycine
-
inhibits cleavage of Pro-Gly
-
N-acetyl-L-methionine
-
strong inhibition at 10 and 50 mM, in the presence of 0.1 mM MnCl2
Ni2+
-
-
NVP LAF237
-
i.e.vildagliptin, IC50: 14219 nM
p-chloromercuribenzoate
p-hydroxymercuribenzoate
phenylmethylsulfonyl fluoride
-
-
phloretin
-
inhibits at 1 mM
phloridzin
-
-
additional information
-
inhibition by high substrate concentrations is observed in cases where the Km is low
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Ala
-
prolinase activity in erythrocytes from both the normal control and the patients with prolidase (EC 3.4.13.9) deficiency is activated
D-Leu
-
enhances activity at concentrations below 20 mM
D-methionine
-
enhances activity at 0-20 mM
D-Val
-
enhances activity at concentrations below 50 mM
DTT
-
activates
Gly
-
prolinase activity in erythrocytes from both the normal control and the patients with prolidase (EC 3.4.13.9) deficiency is activated
glycine
-
-
L-alanine
-
-
Mn2+
-
-
Ser
-
prolinase activity in erythrocytes from both the normal control and the patients with prolidase (EC 3.4.13.9) deficiency is activated
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.42
Ala-Ala-p-nitroanilide
-
-
3.3
Ala-Gly
-
-
0.28 - 1
Ala-Leu
0.12 - 2.72
Ala-Pro-p-nitroanilide
0.027 - 1.673
Arg-Pro-p-nitroanilide
2.05 - 2.668
Asp-Pro-p-nitroanilide
5
carnosine
-
-
21
D-Leu-Gly
-
-
22
Gly-Ala
-
-
29
Gly-Asn
-
tumor enzyme
4.4 - 10
Gly-Ile
21
Gly-L-Ile
-
-
3.16 - 10.6
Gly-L-Leu
20
Gly-L-Val
-
-
0.79 - 10
Gly-Leu
2
Gly-Lys
-
-
2.4 - 10
Gly-Phe
0.48 - 4.599
Gly-Pro-p-nitroanilide
3.6 - 8
Gly-Val
0.33 - 1.25
Leu-Gly
0.25
Leu-Leu
0.25
Leu-Phe
-
-
0.023 - 0.39
Leu-Pro-p-nitroanilide
0.016 - 1.358
Lys-Pro-p-nitroanilide
0.29
Met-Leu
-
-
0.029 - 0.988
Met-Pro-p-nitroanilide
0.47
Pro-Ala
-
at pH 8.0 and 9.2
6.8 - 56.33
Pro-Gly
4.9 - 5.2
Pro-Leu
-
-
4.2 - 46.78
Pro-Met
3.2 - 75.2
Pro-Val
0.238 - 7.462
Ser-Pro-p-nitroanilide
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.7
Ala-Ala-p-nitroanilide
Homo sapiens
-
-
43.3
Ala-Gly
Mus musculus
-
-
33300
Ala-Ile
Mus musculus
-
-
1190 - 6510
Ala-Leu
0.2 - 40
Ala-Pro-p-nitroanilide
0.4 - 14
Arg-Pro-p-nitroanilide
0.9 - 1.6
Asp-Pro-p-nitroanilide
10700 - 23000
Gly-Ile
10900 - 23100
Gly-Leu
8190 - 20400
Gly-Phe
0.2 - 62
Gly-Pro-p-nitroanilide
7450 - 21400
Gly-Val
0.1 - 7
Leu-Pro-p-nitroanilide
0.2 - 3.2
Lys-Pro-p-nitroanilide
0.3 - 15
Met-Pro-p-nitroanilide
0.1 - 19
Ser-Pro-p-nitroanilide
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000024
(1S)-1-cyclohexyl-2-(1,3-dihydro-2H-isoindol-2-yl)-2-oxoethanamine
Homo sapiens
-
IC50: 24 nM
0.003016
(1S)-1-cyclohexyl-2-(3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethanamine
Homo sapiens
-
IC50: 3016 nM
0.001448
(1S)-1-cyclohexyl-2-oxo-2-piperidin-1-ylethanamine
Homo sapiens
-
IC50: 1448 nM
0.000078
(1S)-1-cyclohexyl-2-oxo-2-pyrrolidin-1-ylethanamine
Homo sapiens
-
IC50: 78 nM
0.000019
(2S)-1-[(2S)-2-amino-4-(3,4-dihydroisoquinolin-2(1H)-yl)-4-oxobutanoyl]pyrrolidine-2-carbonitrile
Homo sapiens
-
IC50: 19 nM
0.000016
(2S)-1-[(2S)-2-amino-4-(4-[bis(4-fluorophenyl)methyl]piperazin-1-yl)-4-oxobutanoyl]pyrrolidine-2-carbonitrile
Homo sapiens
-
IC50: 16 nM
0.000027
(2S)-2-amino-2-cyclohexyl-1-[(2R)-2-(iminomethyl)cyclopentyl]ethanone
Homo sapiens
-
IC50: 27 nM
0.000364
(2S,3S)-3-methyl-1-oxo-1-(1,3-thiazolidin-3-yl)pentan-2-amine
Homo sapiens
-
IC50: 364 nM
0.000555
1-(1,3-dihydro-2H-isoindol-2-yl)-4-(3,4-dihydroisoquinolin-2(1H)-yl)-1,4-dioxobutan-2-amine
Homo sapiens
-
IC50: 555 nM
0.00015
1-(1,3-dihydro-2H-isoindol-2-yl)-4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-1,4-dioxobutan-2-amine
Homo sapiens
-
IC50: 150 nM
0.000014
4-(4-[bis(4-fluorophenyl)methyl]piperazin-1-yl)-1-(1,3-dihydro-2H-isoindol-2-yl)-1,4-dioxobutan-2-amine
Homo sapiens
-
IC50: 14 nM
0.004574
6-([2-({2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl}amino)ethyl]amino)nicotinonitrile
Homo sapiens
-
IC50: 4574 nM
0.014219
NVP LAF237
Homo sapiens
-
i.e.vildagliptin, IC50: 14219 nM
1
phloridzin
Rattus norvegicus
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0346
3 - 8
-
-
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5 - 8
-
prolinase II
7.75 - 8.25
-
prolinase I
7.8 - 8.3
-
-
7.8
-
Gly-L-Leu, Gly-L-Val, Gly-L-Ile
8.75
-
pI 4,25
8.8
-
carnosine
additional information
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 8.3
-
about 35% of activity maximum at pH 6,5, activity maximum at pH 7.8-8.3
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
40
-
assay at
45 - 50
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.62
-
calculated from sequence
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
normal and from patients with aortic aneurysms
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
weak expression
Manually annotated by BRENDA team
-
predominantly expressed in testis and pancreas, 5fold higher expression level in human adult than that in fetal testes
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
35000
-
4 * 35000, SDS-PAGE
43800
CPGL-B, calculated from amino acid sequence
45000
-
2 * 45000, SDS-PAGE
52800
CPGL, calculated from amino acid sequence
53000
-
2 * 53000, SDS-PAGE
54000
-
2 * 54000, SDS-PAGE
54200
x * 54200, calculated
57000
-
x * 57000, SDS-PAGE
63000
-
prolinase II, gel filtration
70000
-
gel filtration
76800
-
gel filtration
88000
-
gel filtration
100000
103000
-
x * 103000, calculated from sequence
105000
-
2 * 105000, His-tagged enzyme, SDS-PAGE
107000
-
gel filtration
130000
-
gel filtration
210000
-
His-tagged enzyme, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
-
2 * 105000, His-tagged enzyme, SDS-PAGE
tetramer
-
4 * 35000, SDS-PAGE
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6
-
6 h, 80% loss of activity, ascites tumor enzyme
137178
6.2 - 9
-
6 h stable
137178
6.7
-
6 h, 80% loss of activity, mouse ascites tumor enzyme
137178
7
-
6 h, 25-30% loss of activity, mouse ascites tumor enzyme
137178
7 - 10
-
most stable
137181
7.3 - 8.3
-
maximal stability at 50°C for 30 min
137176
7.5 - 8.5
-
stable
137174
8.1 - 8.3
-
6 h, stable
137178
8.9
-
6 h, 25-30% loss of activity, mouse ascites tumor enzyme
137178
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
-10
-
unstable at
0
-
unstable at
30
-
30 min: stable, 24 h: 40% loss of activity
50
-
pH 7.3-8.3, 30 min, stable
53
-
pH 7.4, about 65% loss of activity after 15 min
additional information
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
addition of 2 mg/ml bovine serum albumin stabilizes the enzyme for assay for 5 min at 40°C
-
dialysis against distilled water causes high degree of inactivation
-
dilute solutions, 0.1 mg/ml in Tris buffer, pH 8.1, of the pure enzyme lose 20% of their activity on standing for one week at 4°C or 2 h at 40°C
-
DTT stabilizes
extremely unstable, even in presence of DTT
-
freezing and thawing without addition of glycerol causes 50% loss of activity
-
Mn2+ stabilizes
-
stabilized to only a limited extent in the presence of 50%-saturated (NH4)2SO4 or 12.5% v/v glycerol
-
stable to 18 h dialysis, at 10°C against 0.02 M phosphate buffer, pH 7.3-8.3
sucrose is necessary for stability
-
very unstable in the absence of Mn2+ or Mg2+
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-30°C, 0.02 M potassium phosphate, pH 8.2, 0.25 M sucrose, stable
-30°C, pH 7.5-8.5, 0.25 M sucrose, stable
-
4°C, lyophilized enzyme stable
-
frozen, in presence of 25% v/v glycerol or 0.2 M sucrose, stable for months
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Ni-NTA column chromatography, Q-Sepharose column chromatography, and Superdex 200 HR gel filtration
-
partial
prolinase I and II
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Sf9 insect cells and 293-T cells
-
expression in Escherichia coli
expression in Sf9 insect cells; overexpression in baculovirus infected Sf9 cells
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
F822A
-
decreased activity
H859A
-
decreased activity
V833A
-
decreased activity
Y844A
-
decreased activity
Show AA Sequence (595 entries)
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