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
3.4.13.9
-
RECOMMENDED NAME
GeneOntology No.
Xaa-Pro dipeptidase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
hydrolysis of Xaa-/-Pro dipeptides; also acts on aminoacyl-hydroxyamine analogues. No action on Pro-Pro
show the reaction diagram
mechanism of substrate specificity and catalysis, overview
-
hydrolysis of Xaa-/-Pro dipeptides; also acts on aminoacyl-hydroxyamine analogues. No action on Pro-Pro
show the reaction diagram
mechanism of substrate specificity and catalysis, detailed overview
-
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
-
-
-
-
hydrolysis of Xaa-/-Pro dipeptides; also acts on aminoacyl-hydroxyproline analogs. No action on Pro-Pro
show the reaction diagram
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
show the reaction diagram
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
show the reaction diagram
catalytic mechanism and active site structure
-
hydrolysis of Xaa-/-Pro dipeptides; also acts on aminoacyl-hydroxyproline analogs. No action on Pro-Pro
show the reaction diagram
catalytic mechanism
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
dipeptide hydrolase
-
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
dipeptidase, proline
-
-
-
-
DPP8
-
-
EC 3.4.3.7
-
-
formerly
-
gamma-peptidase
-
-
-
-
OPAA-2
-
-
OPAA-2
-
-
-
organophosphate acid anhydrolase
-
-
organophosphate acid anhydrolase
-
-
-
organophosphate anhydrolase/prolidase
-
-
organophosphate anhydrolase/prolidase
-
-
-
organophosphorus acid anhydrolase
-
-
organophosphorus acid anhydrolase
-
-
-
PepD
-
-
PepQ
O58885, P81535
-
PepQ
Pyrococcus horikoshii 700860D-5
O58885, P81535
-
-
peptidase D
-
-
-
-
peptidase D
-
-
Pfprol
P81535
-
PH0974
O58691
locus name
PH0974
P81535
-
PH0974
Pyrococcus horikoshii 700860D-5
P81535
-
-
PH0974
Pyrococcus horikoshii DSM 12428
O58691
locus name
-
PH1149
O58885
-
PH1149
Pyrococcus horikoshii 700860D-5
O58885
-
-
Ph1prol
O58691
-
Ph1prol
P81535
-
Ph1prol
Pyrococcus horikoshii DSM 12428
O58691
-
-
Phprol
O58885
-
Phprol
Pyrococcus horikoshii 700860D-5
O58885
-
-
post-proline-cleaving aminopeptidase
-
-
prolidase
-
-
-
-
prolidase
-
;
-
prolidase
-
-
prolidase
-
exopeptidase
prolidase
-
imidodipeptidase
prolidase
-
prolidase hydrolyses dipeptides containing C-terminal proline and hydroxyproline
prolidase
-
-
prolidase
Lactobacillus casei IFPL 731
-
-
-
prolidase
A8WBX8
-
prolidase
Lactococcus lactis NRRL B-1821
A8WBX8
-
-
prolidase
-
-
prolidase
P81535
-
prolidase
O58691
-
prolidase
O58885, O59565, P81535
-
prolidase
Pyrococcus horikoshii 700860D-5
O58885, P81535
-
-
prolidase
Pyrococcus horikoshii DSM 12428
O58691
-
-
prolidase homolog 1
P81535
-
prolidase homolog 1
Pyrococcus horikoshii 700860D-5
P81535
-
-
prolidase homolog 2
O59565
-
prolidase I
-
isozyme
prolidase I
-
-
prolidase II
-
isozyme
prolidase II
-
-
Proline dipeptidase
-
-
-
-
Proline dipeptidase
-
-
Proline dipeptidase
O58885, O59565, P81535
-
Proline dipeptidase
Pyrococcus horikoshii 700860D-5
O58885, P81535
-
-
proline iminopeptidase
-
-
proline-specific amino dipeptidase
-
-
prolyl dipeptidase
-
-
quiescent cell proline dipeptidase
-
-
quiescent cell proline dipeptidase
-
QPP
serum prolidase
-
-
X-Pro dipeptidase
-
-
-
-
imidodipeptidase
-
-
-
-
additional information
-
DPP8 belongs to the family of prolyl dipeptidases
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
additional information
-
the enzyme is a member of the metallopeptidase family
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, with a smaller class of metalloenzymes known as the pita-bread enzymes
additional information
P81535
enzyme belongs to the methionyl amino peptidase family M24, fomerly EC 3.4.3.7
CAS REGISTRY NUMBER
COMMENTARY
9025-32-5
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
strain JD6.5
-
-
Manually annotated by BRENDA team
random source, mixed breed dogs, gene pepQ
-
-
Manually annotated by BRENDA team
; gene PEPD
-
-
Manually annotated by BRENDA team
; patients with non-alcoholic steatohepatitis
-
-
Manually annotated by BRENDA team
comparison of isoforms prolidase I and prolidase II and isoform from patient with enzyme deficiency
-
-
Manually annotated by BRENDA team
comparison of normal human and a patient with prolidase deficiency
-
-
Manually annotated by BRENDA team
expression in Saccharomyces cerevisiae
-
-
Manually annotated by BRENDA team
expression in Saccharomyces cerevisiae, bifunctional enzyme with both dipeptidase and organophosphorus acid anhydrolase activity
-
-
Manually annotated by BRENDA team
healthy individuals and patients with pleural tuberculosis
-
-
Manually annotated by BRENDA team
healthy pregnant women and pregnant women with intrauterine growth restricted infants
-
-
Manually annotated by BRENDA team
patient with enzyme deficiency
-
-
Manually annotated by BRENDA team
patients with enzyme deficiency
-
-
Manually annotated by BRENDA team
patients with postmenopausal osteoporosis
-
-
Manually annotated by BRENDA team
patients with thalassemia major
-
-
Manually annotated by BRENDA team
regulation of enzyme activity and collagen biosynthesis may involve beta1-integrin-dependent signaling
-
-
Manually annotated by BRENDA team
subsp. casei IFPL 731
-
-
Manually annotated by BRENDA team
Lactobacillus casei IFPL 731
-
-
-
Manually annotated by BRENDA team
subsp. bulgaricus CNRZ 397
-
-
Manually annotated by BRENDA team
subsp. lactis DSM 7290
-
-
Manually annotated by BRENDA team
gene pepQ; strain NRRL B-1821, gene pepQ
SwissProt
Manually annotated by BRENDA team
Lactococcus lactis NRRL B-1821
gene pepQ; strain NRRL B-1821, gene pepQ
SwissProt
Manually annotated by BRENDA team
monkey
-
-
Manually annotated by BRENDA team
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
-
-
Manually annotated by BRENDA team
PH0974 or PepQ; strain 700860D-5, gene pepQ, isozyme PH0974 or PepQ
UniProt
Manually annotated by BRENDA team
PH1149 or PepQ; strain 700860D-5, isozyme PH1149
UniProt
Manually annotated by BRENDA team
PH1902; isozyme PH1902
UniProt
Manually annotated by BRENDA team
Pyrococcus horikoshii 700860D-5
PH0974 or PepQ; strain 700860D-5, gene pepQ, isozyme PH0974 or PepQ
UniProt
Manually annotated by BRENDA team
Pyrococcus horikoshii 700860D-5
PH1149 or PepQ; strain 700860D-5, isozyme PH1149
UniProt
Manually annotated by BRENDA team
Pyrococcus horikoshii DSM 12428
-
UniProt
Manually annotated by BRENDA team
isoenzymes PD I and PD II
-
-
Manually annotated by BRENDA team
male Wistar rats, isozymes PD I and PD II
-
-
Manually annotated by BRENDA team
Wistar albino rats
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
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
-
increased PSR activity in case of colitis
malfunction
P12955
misfunctioning causes prolidase deficiency, a recessive connective tissue disorder characterized by severe skin lesions, mental retardation and respiratory tract infections
malfunction
-
decreased serum prolidase activity and increased oxidative stress are correlated in early pregnancy loss, overview
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
-
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
malfunction
-
prolidase may play a role in angiogenesis
malfunction
-
enzyme activity is increased in aortic dilatation compared to controls
metabolism
-
the enzyme is important in the collagen metabolism, overview
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
metabolism
-
prolidase catalyzes the final step of collagen degradation
metabolism
-
prolidase catalyzes the final step of collgane breakdown, releasing free proline for collagen recycling
physiological function
-
OPAA-2 is active in detoxification of organophosphorus compounds, the nerve agents GB, sarin or O-isopropyl methylphosphonofluoridate, VX and blister agent HD, a sulfur mustard, overview
physiological function
-
prolidase is a marker of collagen turnover. Th enezyme activity is higher in women with early pregenancy 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 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 is a specific imidodipeptidase involved in collagen degradation
physiological function
-
prolidase activity may be a step-limiting factor in the regulation of collagen biosynthesis
physiological function
-
OPAA-2 is active in detoxification of organophosphorus compounds, the nerve agents GB, sarin or O-isopropyl methylphosphonofluoridate, VX and blister agent HD, a sulfur mustard, overview
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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 + H2O
Ala + Pro
show the reaction diagram
-
-
-
-
?
Ala-Pro + H2O
Ala + Pro
show the reaction diagram
O58885, O59565, P81535, -
-
-
-
?
Ala-Pro + H2O
Ala + Pro
show the reaction diagram
O58691, -
-
-
-
?
Ala-Pro + H2O
Ala + Pro
show the reaction diagram
-
enzyme-substrate interaction model
-
-
?
Ala-Pro + H2O
Ala + Pro
show the reaction diagram
-
preferred substrate of isozyme PD I
-
-
?
Ala-Pro + H2O
Ala + Pro
show the reaction diagram
-
best substrate of isozyme PD I
-
-
?
Ala-Pro-amino-4-trifluoromethylcoumarin + H2O
alanine + Pro-4-trifluoromethylcoumarin
show the reaction diagram
-
-
-
?
Ala-Pro-amino-4-trifluoromethylcoumarin + H2O
alanine + Pro-4-trifluoromethylcoumarin
show the reaction diagram
-
-
-
?
Ala-Pro-amino-4-trifluoromethylcoumarin + H2O
?
show the reaction diagram
-
-
-
?
Ala-Pro-Gly + H2O
Ala + Pro-Gly
show the reaction diagram
-
-
-
?
Arg-Pro + H2O
Arg + Pro
show the reaction diagram
-
-
-
-
?
Arg-Pro + H2O
Arg + Pro
show the reaction diagram
-
-
-
-
?
Arg-Pro + H2O
Arg + Pro
show the reaction diagram
-
-
-
-
?
Arg-Pro + H2O
Arg + Pro
show the reaction diagram
O58885, O59565, P81535, -
-
-
-
?
Arg-Pro + H2O
Arg + Pro
show the reaction diagram
-
preferred substrate
-
-
?
Arg-Pro + H2O
Arg + Pro
show the reaction diagram
A8WBX8, -
the substrate Leu-Pro is preferred with cofactor zinc, whereas Arg-Pro is preferred with manganese, the enzyme shows an allosteric response to changes in substrate concentrations, with a Hill constant of 1.57 for Arg-Pro
-
-
?
Arg-Pro + H2O
Arg + Pro
show the reaction diagram
Lactococcus lactis NRRL B-1821
A8WBX8
the substrate Leu-Pro is preferred with cofactor zinc, whereas Arg-Pro is preferred with manganese, the enzyme shows an allosteric response to changes in substrate concentrations, with a Hill constant of 1.57 for Arg-Pro
-
-
?
Arg-Pro + H2O
Arg + Pro
show the reaction diagram
Pyrococcus horikoshii 700860D-5
O58885, P81535
-
-
-
?
Asp-Pro + H2O
Asp + Pro
show the reaction diagram
-
-
-
-
?
Gly-Hyp + H2O
Gly + Hyp
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-L-Pro + H2O
Gly + L-Pro
show the reaction diagram
-
-
-
-
?
Gly-L-Pro + H2O
Gly + L-Pro
show the reaction diagram
-
-
-
-
?
Gly-Pro
?
show the reaction diagram
-
-
-
-
-
Gly-Pro + H2O
Glycine + proline
show the reaction diagram
-
-
-
?
Gly-Pro + H2O
Gly + Pro
show the reaction diagram
-
-
-
-
?
Gly-Pro + H2O
Gly + Pro
show the reaction diagram
-
-
-
?
Gly-Pro + H2O
Gly + Pro
show the reaction diagram
-
-
-
?
Gly-Pro + H2O
Gly + Pro
show the reaction diagram
-
-
-
-
?
Gly-Pro + H2O
Gly + Pro
show the reaction diagram
-
-
-
-
r
Gly-Pro + H2O
Gly + Pro
show the reaction diagram
-
-
-
-
?
Gly-Pro + H2O
Gly + Pro
show the reaction diagram
-
-
-
-
?
Gly-Pro + H2O
Gly + Pro
show the reaction diagram
-
-
-
ir
Gly-Pro + H2O
Gly + Pro
show the reaction diagram
-
-
-
ir
Gly-Pro + H2O
Gly + Pro
show the reaction diagram
-
-
-
-
?
Gly-Pro + H2O
Gly + Pro
show the reaction diagram
-
-
-
-
?
Gly-Pro + H2O
Gly + Pro
show the reaction diagram
-
-
-
-
?
Gly-Pro + H2O
Gly + Pro
show the reaction diagram
O58885, O59565, P81535, -
-
-
-
?
Gly-Pro + H2O
Gly + Pro
show the reaction diagram
O58691, -
-
-
-
?
Gly-Pro + H2O
Gly + Pro
show the reaction diagram
-
preferred substrate
-
-
?
Gly-Pro + H2O
Gly + Pro
show the reaction diagram
-
prolidase I activity
-
-
?
Gly-Pro + H2O
Gly + Pro
show the reaction diagram
-
assay at pH 8.0, 37C
-
-
?
Gly-Pro + H2O
Gly + Pro
show the reaction diagram
-
very low activity with isozyme PD II
-
-
?
Gly-Pro + H2O
Gly + Pro
show the reaction diagram
Pyrococcus horikoshii DSM 12428
O58691
-
-
-
?
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
-
-
-
-
-
His-Pro + H2O
His + Pro
show the reaction diagram
-
-
-
-
?
Ile-Pro + H2O
Ile + Pro
show the reaction diagram
-
-
-
-
-
Ile-Pro + H2O
Ile + Pro
show the reaction diagram
-
-
-
-
?
Ile-Pro + H2O
Ile + 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-Ala-Pro + H2O
L-Ala + Pro
show the reaction diagram
-
-
-
-
?
L-Ala-Pro + H2O
L-Ala + Pro
show the reaction diagram
-
-
-
-
?
L-Ala-Pro + H2O
L-Ala + Pro
show the reaction diagram
-
-
-
-
?
L-Ala-Pro + H2O
L-Ala + Pro
show the reaction diagram
-
-
-
-
?
L-Ala-Pro + H2O
L-Ala + Pro
show the reaction diagram
-
-
-
-
?
L-Ala-Pro + H2O
L-Ala + 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-Leu-L-Pro + H2O
L-Leu + L-Pro
show the reaction diagram
-
100% activity in the presence of 1 mM ZnCl2
-
-
?
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-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-Phe-Pro + H2O
L-Phe + Pro
show the reaction diagram
-
-
-
-
?
L-Phe-Pro + H2O
L-Phe + Pro
show the reaction diagram
-
-
-
-
?
L-Phe-Pro + H2O
L-Phe + Pro
show the reaction diagram
-
-
-
-
?
L-Phe-Pro + H2O
L-Phe + Pro
show the reaction diagram
-
-
-
-
?
L-Phe-Pro + H2O
L-Phe + Pro
show the reaction diagram
-
-
-
-
?
L-Phe-Pro + H2O
L-Phe + Pro
show the reaction diagram
-
-
-
-
?
L-Phe-Pro + H2O
L-Phe + Pro
show the reaction diagram
-
prolidase II activity
-
-
-
L-Phe-Pro + H2O
L-Phe + Pro
show the reaction diagram
-
specific for active bond in trans configuration
-
-
?
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
-
-
-
-
?
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
-
-
-
-
?
L-Pro-L-Met + H2O
L-Pro + L-Met
show the reaction diagram
-
-
-
-
?
L-Pro-L-Phe + H2O
L-Pro + L-Phe
show the reaction diagram
-
-
-
-
?
L-Pro-L-Ser + H2O
L-Pro + L-Ser
show the reaction diagram
-
-
-
-
?
L-Pro-L-Val + H2O
L-Pro + L-Val
show the reaction diagram
-
-
-
-
?
L-Val-L-Pro + H2O
L-Val + L-Pro
show the reaction diagram
-
-
-
-
?
L-Val-L-Pro + H2O
L-Val + L-Pro
show the reaction diagram
-
14.4% activity compared to L-Leu-L-Pro, in the presence of 1 mM ZnCl2
-
-
?
L-Val-Pro + H2O
L-Val + Pro
show the reaction diagram
-
-
-
-
?
L-Val-Pro + H2O
L-Val + Pro
show the reaction diagram
-
-
-
-
?
L-Val-Pro + H2O
L-Val + Pro
show the reaction diagram
-
-
-
-
?
L-Val-Pro + H2O
L-Val + 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
-
-
-
-
?
Leu-Pro + H2O
Leu + Pro
show the reaction diagram
-
-
-
-
?
Leu-Pro + H2O
Leu + Pro
show the reaction diagram
-
-
-
-
?
Leu-Pro + H2O
Leu + Pro
show the reaction diagram
-
-
-
-
?
Leu-Pro + H2O
Leu + Pro
show the reaction diagram
-
-
-
-
?
Leu-Pro + H2O
Leu + Pro
show the reaction diagram
-
-
-
-
?
Leu-Pro + H2O
Leu + Pro
show the reaction diagram
-
-
-
-
?
Leu-Pro + H2O
Leu + Pro
show the reaction diagram
-
-
-
-
?
Leu-Pro + H2O
Leu + Pro
show the reaction diagram
-
-
-
-
?
Leu-Pro + H2O
Leu + Pro
show the reaction diagram
-
-
-
-
?
Leu-Pro + H2O
Leu + Pro
show the reaction diagram
-
-
-
-
?
Leu-Pro + H2O
Leu + Pro
show the reaction diagram
O58691, -
-
-
-
?
Leu-Pro + H2O
Leu + Pro
show the reaction diagram
O58885, O59565, P81535, -
high activity
-
-
?
Leu-Pro + H2O
Leu + Pro
show the reaction diagram
A8WBX8, -
the substrate Leu-Pro is preferred with cofactor zinc, whereas Arg-Pro is preferred with manganese, the enzyme shows an allosteric response to changes in substrate concentrations, with a Hill constant of 1.53 for Leu-Pro
-
-
?
Leu-Pro + H2O
Leu + Pro
show the reaction diagram
Pyrococcus horikoshii DSM 12428
O58691
-
-
-
?
Leu-Pro + H2O
Leu + Pro
show the reaction diagram
Lactococcus lactis subsp. cremoris AM2
-
-
-
-
?
Leu-Pro + H2O
Leu + Pro
show the reaction diagram
Lactococcus lactis NRRL B-1821
A8WBX8
the substrate Leu-Pro is preferred with cofactor zinc, whereas Arg-Pro is preferred with manganese, the enzyme shows an allosteric response to changes in substrate concentrations, with a Hill constant of 1.53 for Leu-Pro
-
-
?
Leu-Pro + H2O
Leu + Pro
show the reaction diagram
Pyrococcus horikoshii 700860D-5
O58885, P81535
high activity
-
-
?
Lys-Pro + H2O
Lys + Pro
show the reaction diagram
-
-
-
-
?
Lys-Pro + H2O
Lys + Pro
show the reaction diagram
-
-
-
-
?
Lys-Pro + H2O
Lys + Pro
show the reaction diagram
A8WBX8, -
-
-
-
?
melphalan + H2O
?
show the reaction diagram
-
-, prolidase-dependence of prodrug cytotoxicity in the cell lines compared to that of the parent drug, melphalan, overview
-
-
?
Met-Pro + H2O
Met + Pro
show the reaction diagram
-
-
-
-
?
Met-Pro + H2O
Met + Pro
show the reaction diagram
-
-
-
-
?
Met-Pro + H2O
Met + Pro
show the reaction diagram
-
-
-
-
?
Met-Pro + H2O
Met + Pro
show the reaction diagram
-
-
-
-
?
Met-Pro + H2O
Met + Pro
show the reaction diagram
O58691, -
-
-
-
?
Met-Pro + H2O
Met + Pro
show the reaction diagram
O58885, O59565, P81535, -
best substrate
-
-
?
Met-Pro + H2O
Met + Pro
show the reaction diagram
-
high activity
-
-
?
Met-Pro + H2O
Met + Pro
show the reaction diagram
-
preferred substrate of isozyme PD II
-
-
?
Met-Pro + H2O
Met + Pro
show the reaction diagram
-
best substrate of isozyme PD II
-
-
?
Met-Pro + H2O
Met + Pro
show the reaction diagram
-
preferred substrate of wild-type and mutant enzymes
-
-
?
Met-Pro + H2O
Met + Pro
show the reaction diagram
Pyrococcus horikoshii DSM 12428
O58691
-
-
-
?
Met-Pro + H2O
Met + Pro
show the reaction diagram
Pyrococcus horikoshii 700860D-5
O58885, P81535
best substrate
-
-
?
Phe-Pro + H2O
Phe + Pro
show the reaction diagram
-
-
-
-
?
Phe-Pro + H2O
Phe + Pro
show the reaction diagram
-
-
-
-
?
Phe-Pro + H2O
Phe + Pro
show the reaction diagram
-
-
-
-
?
Phe-Pro + H2O
Phe + Pro
show the reaction diagram
-
-
-
-
?
Phe-Pro + H2O
Phe + Pro
show the reaction diagram
A8WBX8, -
-
-
-
?
Phe-Pro + H2O
Phe + Pro
show the reaction diagram
O58885, O59565, P81535, -
-
-
-
?
Phe-Pro + H2O
Phe + Pro
show the reaction diagram
O58691, -
-
-
-
?
Phe-Pro + H2O
Phe + Pro
show the reaction diagram
Pyrococcus horikoshii DSM 12428
O58691
-
-
-
?
Phe-Pro + H2O
Phe + Pro
show the reaction diagram
Lactococcus lactis NRRL B-1821
A8WBX8
-
-
-
?
Pro-Ala + H2O
Pro + Ala
show the reaction diagram
-
-
-
-
?
Pro-Ala + H2O
Pro + Ala
show the reaction diagram
O58885, O59565, P81535, -
very low activity
-
-
?
Pro-Ala + H2O
Pro + Ala
show the reaction diagram
Pyrococcus horikoshii 700860D-5
O58885, P81535
very low activity
-
-
?
Pro-Hyp + H2O
Pro + Hyp
show the reaction diagram
-
-
-
-
?
Pro-Hyp + H2O
Pro + Hyp
show the reaction diagram
-
-
-
-
?
Pro-Pro + H2O
Pro + Pro
show the reaction diagram
-
-
-
-
?
Pro-Pro + H2O
Pro + Pro
show the reaction diagram
-
-
-
-
-
Pro-Pro + H2O
Pro + Pro
show the reaction diagram
-
-
-
-
?
Pro-Pro + H2O
Pro + Pro
show the reaction diagram
-
-
-
-
?
Pro-Pro + H2O
Pro + Pro
show the reaction diagram
-
substrate of isozyme PD II, negligible activity with isozyme PD I
-
-
?
prophalan-D + H2O
?
show the reaction diagram
-
-, 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
?
show the reaction diagram
-
-
-
-
?
prophalan-L + H2O
?
show the reaction diagram
-
the L-proline prodrug of melphalan
-
-
?
prophalan-L + H2O
?
show the reaction diagram
-
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
-
-
?
Ser-Pro + H2O
Ser + Pro
show the reaction diagram
-
-
-
-
?
Ser-Pro + H2O
Ser + Pro
show the reaction diagram
-
-
-
-
?
Ser-Pro + H2O
Ser + Pro
show the reaction diagram
-
-
-
-
?
Ser-Pro + H2O
Ser + Pro
show the reaction diagram
-
preferred substrate of isozyme PD I
-
-
?
Ser-Pro + H2O
Ser + Pro
show the reaction diagram
-
best substrate of isozyme PD I
-
-
?
soman + H2O
?
show the reaction diagram
-
organophosphorus acid anhydrolase activity
-
-
?
Thr-Pro + H2O
Thr + Pro
show the reaction diagram
-
-
-
-
?
Thr-Pro + H2O
Thr + Pro
show the reaction diagram
-
-
-
-
?
Tyr-Pro + H2O
Tyr + Pro
show the reaction diagram
-
-
-
-
?
Val-Pro + H2O
Val + Pro
show the reaction diagram
-
-
-
-
?
Val-Pro + H2O
Val + Pro
show the reaction diagram
-
-
-
-
?
Val-Pro + H2O
Val + Pro
show the reaction diagram
-
-
-
-
?
Val-Pro + H2O
Val + Pro
show the reaction diagram
A8WBX8, -
-
-
-
?
Val-Pro + H2O
Val + Pro
show the reaction diagram
O58691, -
-
-
-
?
Val-Pro + H2O
Val + Pro
show the reaction diagram
Pyrococcus horikoshii DSM 12428
O58691
-
-
-
?
Val-Pro + H2O
Val + Pro
show the reaction diagram
Lactococcus lactis NRRL B-1821
A8WBX8
-
-
-
?
Xaa-Pro + H2O
Xaa + Pro
show the reaction diagram
P81535
-
-
?
Met-Pro + H2O
L-Met + L-Pro
show the reaction diagram
-
68% of the activity with Gly-L-Pro
-
-
?
additional information
?
-
-
-
-
-
-
additional information
?
-
-
guinea pig brain: general dipeptidase and prolinase activity, enzyme also acts on hydroxyproline dipeptides and amides
-
-
-
additional information
?
-
-
no substrate: Pro-Pro, Gly-Pro
-
-
-
additional information
?
-
-
no substrate: Pro-Pro, Gly-Pro
-
-
-
additional information
?
-
O58885, O59565, P81535, -
substrate specificity, overview
-
-
-
additional information
?
-
-
cleaves imidodipeptides with C-terminal proline or hydroxyproline
-
?
additional information
?
-
-
substrate specificity of isozymes, overview
-
-
-
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 catalyzes the stereoselective hydrolysis of organophosphate triesters and organophosphate diesters such as (S)-methyl phenyl 4-nitrophenyl phosphate with 70fold preferrence for the (S)-enantiomer. Enzyme hydrolyzes 4-nitrophenyl analogs of sarin, soman, and VX
-
-
-
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
?
-
-
lack of prolidase I leads to prolidase deficiency, a disease characterized by intractable skin lesions, recurrent respiratory infections, and mental retardation, physiologic roles of prolidase isoenzymes, PD I functions by way of an intestinal peptide carrier, which may be regulated by the uptake of various iminodipeptides, intestinal PD II also participates in absorption of proline and other amino acids early in life, overview
-
-
-
additional information
?
-
-
PepQ is a cytoplasmic prolidase that specifically liberated proline from dipeptides with increased activity under high salt conditions, PepX, a X-prolyl-dipeptidyl aminopeptidase, and PepI, a iminopeptidase, are unaffected, 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, 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
?
-
-
no or poor activity with prophalan-D and melphalan
-
-
-
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
?
-
A8WBX8, -
substrate specificity, dependent on the catalytic metal cation, overview, no activity with Pro-Pro, Glu-Pro, Gly-Pro, Asp-Pro, Leu-Leu-Pro, and Leu-Val-Pro, molecular modeling, overview
-
-
-
additional information
?
-
-
substrate specificity, prolidase is a cytosolic imidodipeptidase, which specifically splits imidodipeptides with C-terminal proline or hydroxyproline, overview
-
-
-
additional information
?
-
-
prolidase plays an important role in collagen biosynthesis
-
-
-
additional information
?
-
-
does not degrade L-Glu-L-Pro, Gly-L-Pro, L-Pro-L-Pro, L-Leu-L-Leu-L-Pro, L-Leu-L-Val-L-Pro, and L-Asp-L-Pro
-
-
-
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
?
-
P12955
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
?
-
-
OPAA-2 can hydrolyze organophosphorus acid nerve agents, such as sarin and soman. OPAA-2 has been reclassified as a prolidase because it can also efficiently hydrolyze X-Pro dipeptides. The enzyme OPAA-2 shows activity with P-F, P-C and P-O bonds. It can also preferentially cleave the dipeptides Leu-Pro and Ala-Pro and is specific for dipeptides with proline in the C-terminal position, but shows no activity with the substrates Pro-Leu and Pro-Gly
-
-
-
additional information
?
-
-
Pfprol has a narrow substrate specificity, only hydrolyzing dipeptides with a proline in the C-terminus and nonpolar amino acids, Leu, Met, Val, Phe, or Ala, in the N-terminal position. Pfprol cannot cleave dipeptides with proline in the N-terminus. Substrate binding, structure-function relationship, overview. No activity on organophosphorus nerve agents sarin, cyclosarin, and soman, but with diisopropyl phosphorofluoridate
-
-
-
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
-
-
-
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 bifunctional enzyme is active on the nerve agent organophosphate substrate diisopropyl fluorophosphate, DFP, producing N,N'-diisopropyldiamidophosphate, binding structure modelling, overview
-
-
-
additional information
?
-
-
the enzyme from guinea pig brain can also cleave substrates without a prolyl residue
-
-
-
additional information
?
-
-
the enzyme from Lactococcus casei can also cleave substrates without a prolyl residue
-
-
-
additional information
?
-
-
the enzyme is also active with diisopropyl phosphorofluoridate, an organophosphorus nerve reagent
-
-
-
additional information
?
-
-
the enzyme only hydrolyzes dipeptides with a proline in the C-terminus and cannot cleave dipeptides with proline in the N-terminus
-
-
-
additional information
?
-
-
wild-type Lactococcus lactis prolidase preferably hydrolyzes Xaa-Pro dipeptides where Xaa is a hydrophobic amino acid. Anionic Glu-Pro and Asp-Pro dipeptides cannot be hydrolyzed at any observable rates, and the hydrolysis of cationic Arg-Pro and Lys-Pro dipeptides is at about one tenth of the rate of Leu-Pro, no activity with tripeptides Leu-Leu-Pro and Leu-Val-Pro, substrate specificity of wild-type and mutant enzymes, the enzyme activity depends highly on the metal ion, overview
-
-
-
additional information
?
-
Lactobacillus casei IFPL 731
-
the enzyme from Lactococcus casei can also cleave substrates without a prolyl residue
-
-
-
additional information
?
-
Lactococcus lactis NRRL B-1821
A8WBX8
substrate specificity, dependent on the catalytic metal cation, overview, no activity with Pro-Pro, Glu-Pro, Gly-Pro, Asp-Pro, Leu-Leu-Pro, and Leu-Val-Pro, molecular modeling, overview
-
-
-
additional information
?
-
Pyrococcus horikoshii 700860D-5
O58885, P81535
substrate specificity, overview
-
-
-
additional information
?
-
-
OPAA-2 can hydrolyze organophosphorus acid nerve agents, such as sarin and soman. OPAA-2 has been reclassified as a prolidase because it can also efficiently hydrolyze X-Pro dipeptides. The enzyme OPAA-2 shows activity with P-F, P-C and P-O bonds. It can also preferentially cleave the dipeptides Leu-Pro and Ala-Pro and is specific for dipeptides with proline in the C-terminal position, but shows no activity with the substrates Pro-Leu and Pro-Gly
-
-
-
additional information
?
-
-
the bifunctional enzyme is active on the nerve agent organophosphate substrate diisopropyl fluorophosphate, DFP, producing N,N'-diisopropyldiamidophosphate, binding structure modelling, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
Gly-Pro
?
show the reaction diagram
-
-
-
-
-
Gly-Pro + H2O
Glycine + proline
show the reaction diagram
-
-
-
?
prophalan-D + H2O
?
show the reaction diagram
-
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
?
show the reaction diagram
-
the L-proline prodrug of melphalan
-
-
?
prophalan-L + H2O
?
show the reaction diagram
-
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
-
-
?
melphalan + H2O
?
show the reaction diagram
-
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
?
-
-
lack of prolidase I leads to prolidase deficiency, a disease characterized by intractable skin lesions, recurrent respiratory infections, and mental retardation, physiologic roles of prolidase isoenzymes, PD I functions by way of an intestinal peptide carrier, which may be regulated by the uptake of various iminodipeptides, intestinal PD II also participates in absorption of proline and other amino acids early in life, overview
-
-
-
additional information
?
-
-
PepQ is a cytoplasmic prolidase that specifically liberated proline from dipeptides with increased activity under high salt conditions, PepX, a X-prolyl-dipeptidyl aminopeptidase, and PepI, a iminopeptidase, are unaffected, 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, 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 plays an important role in collagen biosynthesis
-
-
-
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 ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
-
stimulation
Ca2+
-
can substitute for Mn2+ by less than 30%
Co2+
-
stimulation
Co2+
-
requires Co2+ in addition to one cobalt atom bound per subunit
Co2+
-
dinuclear metal cluster in the active site, binding of 2 Co2+ per subunit
Co2+
-
one Co-bound dinuclear metal cluster per monomer, Co1 is the tight binding, Co2 the loose binding metal center. Wild-type exhibits maximal activity in presence of 0.5 mM Co2+, less than 20% residual activity with 10 mM Co2+
Co2+
-
metalloenzyme, required for activity, a homodimer having one Co-bound dinuclear metal cluster per monomer with one tightly bound Co1 and one loosely bound Co2 cobalt site, 5 amino acids that function as metal-binding residues: His284 and Glu313 solely bind to the first cobalt centre, Co1, Asp209 to the second cobalt centre, Co2, and Asp220 and Glu327 to both Co2+ ions
Co2+
-
can substitute for Mn2+ by less than 30%
Co2+
-
activates, preferred metal ion
Co2+
-
highly activating, one Co2+ per enzyme subunit
Co2+
O58885, O59565, P81535, -
dependent on; dependent on; dependent on
Co2+
-
activates
Cobalt
-
2 atoms per subunit are required for optimum activity
Cu2+
O58885, O59565, P81535, -
activates; activates
Fe2+
-
best activating divalent ion
Fe2+
O58885, O59565, P81535, -
activates; activates
Fe3+
-
stimulation
Mg2+
-
stimulation
Mg2+
-
can substitute for Mn2+ by less than 30%
Mn2+
-
requirement
Mn2+
-
requirement
Mn2+
-
stimulation
Mn2+
-
requirement
Mn2+
-
requirement
Mn2+
-
stimulation
Mn2+
-
no stimulation
Mn2+
-
stimulation
Mn2+
-
Co2+ can be replaced by Mn2+
Mn2+
-
dependent on, metallopeptidase, complex formation with anthracyclines
Mn2+
-
stimulation
Mn2+
-
stabilization of enzyme against inhibition by Ni2+
Mn2+
-
metalloenzyme, required for activity, each subunit contains two ions Mn2+, binding structure, overview; 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
Mn2+
-
dependent on, best divalent cation
Mn2+
A8WBX8, -
two preferred metal cations: zinc and manganese, the substrate Leu-Pro is preferred with zinc, whereas Arg-Pro is preferred with manganese
Mn2+
-
required for enzyme activation
Mn2+
-
required
Mn2+
-
required
Mn2+
-
dependent on
Mn2+
-
required for activity
Mn2+
-
40 mM, dependent on
Mn2+
-
activation of prolidase requires preincubation with 2 mM Mn2+
Mn2+
-
requires divalent cations for activity, most active with manganese
Mn2+
-
activates
Mn2+
-
requires divalent cations for activity, most active with manganese
Mn2+
-
activates
Mn2+
-
requires divalent cations for activity, most active with manganese
Mn2+
O58885, O59565, P81535, -
activates; activates
Mn2+
-
the enzyme harbors binuclear Mn2+ ions within the active site
Mn2+
-
activates
Mn2+
-
activates
Mn2+
P12955
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
Mn2+
-
required
Mn2+
-
dependent on
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+
O58885, O59565, P81535, -
activates; activates
Zn2+
-
requirement
Zn2+
-
2 Zn2+ bound to the subunit in the crystallized enzyme only replacing the Co2+ ions, binding structure via 5 coordinates
Zn2+
-
can substitute for Mn2+ by less than 30%
Zn2+
A8WBX8, -
two preferred metal cations: zinc and manganese, the substrate Leu-Pro is preferred with zinc, whereas Arg-Pro is preferred with manganese
Zn2+
-
required for optimum activity
Zn2+
-
requires divalent cations for activity, most active with zinc
Zn2+
-
interaction with amino acid residues D209, D220, H284, E313 and E327, overview
Zn2+
O58885, O59565, P81535, -
activates; activates
Zn2+
-
activates
Zn2+
P12955
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
Mn2+
-
activates
additional information
A8WBX8, -
the substrate specificity is dependent on the catalytic metal cation, molecular modeling, overview
additional information
-
PepQ shows increased activity under high salt conditions
additional information
-
OPAA-2 has a conserved binuclear metal center
additional information
-
the enzyme requires divalent cations for activity
additional information
-
the enzyme contains a dinuclear metal center bridged by a water molecule or hydroxide ion. The metal cluster is essential for the activation of catalysis. It functions to activate a nucleophile for the reaction, as well as participating in substrate binding and stabilizing the transition state. The dipeptidase is maximally active with the addition of the divalent cations Co2+ and Mn2+ and it cannot be substituted with other divalent cations, i.e Mg2+, Ca2+, Fe2+, Ni2+, Cu2+, or Zn2+, under aerobic conditions
additional information
P12955
determination of enzyme samples metal contents, overview
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(2S,3R)-3-amino-2-hydroxy-5-methyl-hexanoyl-proline
-
-
(2S,3R)-3-amino-2-hydroxy-5-methylhexanoyl-proline
-
-
1,10-phenanthroline
-
-
1,10-phenanthroline
-
-
1,10-phenanthroline
-
-
1,10-phenanthroline
-
-
1,10-phenanthroline
-
-
1,2-Cylcopentanedicarboxylic acid
-
-
2-mercaptoethanol
-
-
2-mercaptoethanol
-
-
2-mercaptoethanol
-
weakly
2-mercaptoethanol
-
1 mM, 55% residual activity
acetic acid
-
inhibts the enzyme in colonic tissue, but not in plasma
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
Captopril
-
inhibits isozyme PD I dose-dependently, but shows no inhibition of isozyme PD II at 0.1 mM
carmustine
-
-
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
Cu2+
-
strong
Cupferron
-
N-Hydroxy-N-nitrosobenzeneamine ammonium salt
D,L-4-Amino-4-phosphonobutyrate
-
-
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
-
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
-
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
-
EDTA
-
1 mM, 70% residual activity
Gly-PSI[CO-CH]-Pro
-
-
iodoacetamide
-
-
iodoacetate
-
-
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-proline
-
competitive
L-valine
-
inhibitory to enzyme isoform prolidase I, activating isoform prolidase II
L-valinyl-D-boroproline
-
-
melanin
-
30% inhibition at 0.1 mg/ml, reverses inhibition of prolidase by netilmicin
N,N'-diisopropyldiamidofluorophosphate
-
i.e. DDFP or mipafox
N-acetylproline
-
-
N-Benzyloxycarbonyl-L-proline
-
-
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
-
daily injection of inhibitor for 3 weeks results in significant reduction of enzyme activity in erythrocyte. Inhibitor is not degraded in vivo
N-Benzyloxycarbonyl-L-proline
-
50% inhibition at 5 mM
N-Benzyloxycarbonyl-L-proline
-
-
N-Benzyloxycarbonyl-L-proline
-
inhibits isozyme PD I dose-dependently, but shows no inhibition of isozyme PD II at up to 1 mM
N-Benzyloxycarbonyl-L-proline
-
competitive, 60-83% inhibition levels of the enzyme from different cancer cell lines, overview
N-Benzyloxycarbonyl-L-proline
-
competitive
N-Benzyloxycarbonyl-L-proline
-
inhibits PD I, but not PD II
N-[N'-(2-bromoethyl)-N'-nitrosocarbamoyl]-L-proline
-
-
netilmicin
-
80% inhibition at 0.01 mM, reversible by melanin
Ni2+
-
Ni2+ (0.05 and 0.15mM) is a competitive inhibitor of prolidase with respect to Mn2+
NiCl2
-
specific inhibition of enzyme activity in situ. Increasing concentration of Mn2+ stabilizes against Ni2+ inhibition
NiCl2
-
inhibits isozye PD II much more effectively than isozyme PD I
p-chloromercuribenzoate
-
-
p-chloromercuribenzoate
-
-
p-chloromercuribenzoate
-
-
p-chloromercuribenzoate
-
-
p-chloromercuribenzoate
-
-
p-chloromercuribenzoate
-
-
p-chloromercuribenzoate
-
-
p-hydroxymercuribenzoate
-
-
p-hydroxymercuribenzoate
-
-
p-hydroxymercuribenzoate
-
-
p-hydroxymercuribenzoate
-
-
paracetamol
-
mechanism of PLD inhibition by paracetamol is noncompetitive inhibition
Phenacetin
-
-
phenylacetyl-thioproline
-
-
phosphoenolpyruvate
-
-
Phosphonates
-
-
Phosphonocarboxylates
-
-
-
sodium salicylate
-
-
-
trans-1,2-cyclopentanedicarboxylate
-
-
Z-Pro
-
roughly 80% inhibition at 2.53 mM
Zn2+
-
slightly
Zn2+
-
slightly
Zn2+
-
slightly
Zn2+
-
slightly
Zn2+
-
strong
additional information
-
insensitive to EDTA
-
additional information
-
mechanism of inhibition
-
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 ACCESSION NO.
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
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
-
activation of activity against substrates L-Pro-L-Ala, L-Pro-L-Val, L-Pro-L-Met, and L-Pro-L-Asp
glycine
-
activation of isoforms prolidase I and prolidase II
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
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-donors such as SIN I and DETA/NO increase enzyme activity in time- and dose-dependent manner. Enzyme activity also increases upon transfection of cells with iNOS. Increased enzymic activity is accompanied by increase in serine/threonine phosphorylation of enzyme
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
-
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
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]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.127
-
Ala-Pro
-
pH 7.8, 37C, recombinant His-tagged wild-type enzyme
0.61
-
Ala-Pro
-
-
1.495
-
Ala-Pro
-
pH 7.8, 37C, recombinant His-tagged mutant F822A
2.219
-
Ala-Pro
-
pH 7.8, 37C, recombinant His-tagged mutant V833A
2.397
-
Ala-Pro
-
pH 7.8, 37C, recombinant His-tagged mutant Y844A
2.72
-
Ala-Pro
-
pH 7.8, 37C, recombinant His-tagged mutant H859A
6
-
Ala-Pro
-
-
8.3
-
Ala-Pro
-
native prolidase
6.7
-
Gly-Hyp
-
-
1.64
-
Gly-L-Pro
-
pH 7.8, 37C, presence of 20 mM glycine, prolidase I
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 37C
2.3
-
Gly-L-Pro
-
pH 7.8, 37C, presence of 20 mM D-valine, prolidase I
2.59
-
Gly-L-Pro
-
pH 7.8, 37C, prolidase I
2.63
-
Gly-L-Pro
-
pH 7.8, 37C, presence of 20 mM L-valine, prolidase I
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 37C
0.006
-
Gly-Pro
-
-
0.14
-
Gly-Pro
-
-
0.14
-
Gly-Pro
-
-
1.3
-
Gly-Pro
-
-
2.88
2.9
Gly-Pro
-
prolidase I from normal human and mother of patient with prolidase deficiency
7.1
-
Gly-Pro
-
-
7.1
-
Gly-Pro
-
-
0.39
-
His-Pro
-
-
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 37C
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 37C
1.7
-
L-Leu-L-Pro
-
mutant enzyme S307G, in 20 mM sodium citrate (pH 6.5), and 1 mM ZnCl2, at 50C
8
-
L-Leu-L-Pro
-
wild type enzyme, in 20 mM sodium citrate (pH 6.5), and 1 mM ZnCl2, at 50C
10.1
-
L-Leu-L-Pro
-
mutant enzyme R293S/S307G, in 20 mM sodium citrate (pH 6.5), and 1 mM ZnCl2, at 50C
14.7
-
L-Leu-L-Pro
-
mutant enzyme S307R, in 20 mM sodium citrate (pH 6.5), and 1 mM ZnCl2, at 50C
18
-
L-Leu-L-Pro
-
mutant enzyme S307D, in 20 mM sodium citrate (pH 6.5), and 1 mM ZnCl2, at 50C
23.3
-
L-Leu-L-Pro
-
mutant enzyme R293S, in 20 mM sodium citrate (pH 6.5), and 1 mM ZnCl2, at 50C
4.11
-
L-Met-L-Pro
-
pH 7.8, 37C, presence of 20 mM glycine, prolidase I
4.43
-
L-Met-L-Pro
-
pH 7.8, 37C, presence of 20 mM glycine, enzyme from patient with enzyme deficiency
4.65
-
L-Met-L-Pro
-
pH 7.8, 37C, presence of 20 mM D-valine, prolidase I
5.39
-
L-Met-L-Pro
-
pH 7.8, 37C, presence of 20 mM glycine, prolidase II
5.48
-
L-Met-L-Pro
-
pH 7.8, 37C, presence of 20 mM L-valine, enzyme from patient with enzyme deficiency
5.65
-
L-Met-L-Pro
-
pH 7.8, 37C, presence of 20 mM L-valine, prolidase II
6.16
-
L-Met-L-Pro
-
pH 7.8, 37C, presence of 20 mM D-valine, enzyme from patient with enzyme deficiency
6.33
-
L-Met-L-Pro
-
pH 7.8, 37C, presence of 20 mM D-valine, prolidase II
8.83
-
L-Met-L-Pro
-
pH 7.8, 37C, presence of 20 mM L-valine, prolidase I
9.2
-
L-Met-L-Pro
-
pH 7.8, 37C, prolidase I
9.65
-
L-Met-L-Pro
-
pH 7.8, 37C, prolidase II
9.89
-
L-Met-L-Pro
-
pH 7.8, 37C, enzyme from patient with enzyme deficiency
6.8
-
L-Pro-Gly
-
pH 7.8, 37C, presence of 0.1 mM MnCl2 plus 20 mM glycine
8.6
-
L-Pro-Gly
-
pH 7.8, 37C, presence of 0.1 mM MnCl2 plus 20 mM glycine, enzyme from patient with enzyme deficiency
9.7
-
L-Pro-Gly
-
pH 7.8, 37C, presence of 0.1 mM MnCl2, enzyme from patient with enzyme deficiency
13.8
-
L-Pro-Gly
-
pH 7.8, 37C, presence of 0.1 mM MnCl2
15.1
-
L-Pro-Gly
-
pH 7.8, 37C, presence of 20 mM glycine
16.7
-
L-Pro-Gly
-
pH 7.8, 37C, presence of 20 mM glycine, enzyme from patient with enzyme deficiency
18.2
-
L-Pro-Gly
-
pH 7.8, 37C, enzyme from patient with enzyme deficiency
26.9
-
L-Pro-Gly
-
pH 7.8, 37C
4.2
-
L-Pro-L-Met
-
pH 7.8, 37C, presence of 20 mM glycine, enzyme from patient with enzyme deficiency
5
-
L-Pro-L-Met
-
pH 7.8, 37C, presence of 0.1 mM MnCl2 plus 20 mM glycine, enzyme from patient with enzyme deficiency
8.1
-
L-Pro-L-Met
-
pH 7.8, 37C, enzyme from patient with enzyme deficiency
8.35
-
L-Pro-L-Met
-
pH 7.8, 37C, presence of 20 mM glycine
9.7
-
L-Pro-L-Met
-
pH 7.8, 37C, presence of 0.1 mM MnCl2, enzyme from patient with enzyme deficiency
9.9
-
L-Pro-L-Met
-
pH 7.8, 37C, presence of 0.1 mM MnCl2 plus 20 mM glycine
17.6
-
L-Pro-L-Met
-
pH 7.8, 37C
19.1
-
L-Pro-L-Met
-
pH 7.8, 37C, presence of 0.1 mM MnCl2
3.2
-
L-Pro-L-Val
-
pH 7.8, 37C, presence of 20 mM glycine, enzyme from patient with enzyme deficiency
5.5
-
L-Pro-L-Val
-
pH 7.8, 37C, presence of 0.1 mM MnCl2 plus 20 mM glycine, enzyme from patient with enzyme deficiency
7.9
-
L-Pro-L-Val
-
pH 7.8, 37C, enzyme from patient with enzyme deficiency
10.1
-
L-Pro-L-Val
-
pH 7.8, 37C, presence of 0.1 mM MnCl2, enzyme from patient with enzyme deficiency
14.7
-
L-Pro-L-Val
-
pH 7.8, 37C, presence of 20 mM glycine
17.3
-
L-Pro-L-Val
-
pH 7.8, 37C, presence of 0.1 mM MnCl2 plus 20 mM glycine
26
-
L-Pro-L-Val
-
pH 7.8, 37C
28.6
-
L-Pro-L-Val
-
pH 7.8, 37C, presence of 0.1 mM MnCl2
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 37C
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 37C
0.2
-
Leu-Pro
-
-
0.81
-
Leu-Pro
O58691, -
pH 7.0, 70C, mutant enzyme A195T/G306S
0.82
-
Leu-Pro
-
-
0.92
-
Leu-Pro
O58691, -
pH 7.0, 70C, wild-type enzyme
0.98
-
Leu-Pro
O58691, -
pH 7.0, 70C, mutant enzyme E127G/E252D
1.3
-
Leu-Pro
-
-
1.6
-
Leu-Pro
O58691, -
pH 7.0, 70C, mutant enzyme E36V
2.92
-
Leu-Pro
O58691, -
pH 7.0, 70C, mutant enzyme Y301C/K342N
3
-
Leu-Pro
-
native prolidase
10.4
-
Leu-Pro
-
human fibroplasts with prolidase deficiency
0.81
-
Met-Pro
-
-
0.81
-
Met-Pro
-
-
1.9
-
Met-Pro
O58885, O59565, P81535, -
pH 7.0, 100C
2.8
-
Met-Pro
-
native prolidase
3.3
-
Met-Pro
-
recombinant prolidase
3.4
-
Met-Pro
O58885, O59565, P81535, -
pH 7.0, 100C
5.7
-
Met-Pro
-
pH 7.0, 70C, recombinant wild-type enzyme; pH 7.0, 70C, wild-type enzyme
6.4
-
Met-Pro
-
pH 7.0, 35C, recombinant wild-type enzyme; pH 7.0, 35C, wild-type enzyme
6.8
-
Met-Pro
-
pH 7.0, 70C, recombinant mutant G39E; pH 7.0, 70C, wild-type enzyme G39E
7.5
-
Met-Pro
-
pH 7.0, 70C, mutant enzyme R19G/G39E/K71E/S229T; pH 7.0, 70C, recombinant mutant R19G/G39E/K71E/S229T
7.9
-
Met-Pro
-
pH 7.0, 35C, mutant enzyme R19G/G39E/K71E/S229T; pH 7.0, 35C, recombinant mutant R19G/G39E/K71E/S229T
7.95
-
Met-Pro
-
pH 7.0, 100C, recombinant wild-type enzyme; pH 7.0, 100C, wild-type enzyme
9.2
-
Met-Pro
-
pH 7.0, 70C, mutant enzyme R19G/K71E/S229T; pH 7.0, 70C, recombinant mutant R19G/K71E/S229T
11.1
-
Met-Pro
-
pH 7.0, 100C, mutant enzyme R19G/G39E/K71E/S229T; pH 7.0, 100C, recombinant mutant R19G/G39E/K71E/S229T
11.3
-
Met-Pro
-
pH 7.0, 35C, mutant enzyme R19G/K71E/S229T; pH 7.0, 35C, recombinant mutant R19G/K71E/S229T
13
-
Met-Pro
-
pH 7.0, 35C, mutant enzyme G39E; pH 7.0, 35C, recombinant mutant G39E
13.7
-
Met-Pro
-
pH 7.0, 100C, mutant enzyme R19G/K71E/S229T; pH 7.0, 100C, recombinant mutant R19G/K71E/S229T
0.76
-
Phe-Pro
-
-
6
-
Phe-Pro
-
-
20
-
Phe-Pro
-
native prolidase
12.5
-
Pro-Hyp
-
-
0.38
-
Pro-Pro
-
-
0.06
-
Val-Pro
-
-
0.41
-
Val-Pro
-
-
4.2
-
Val-Pro
-
native prolidase
14.5
-
Met-Pro
-
pH 7.0, 100C, recombinant mutant G39E; pH 7.0, 100C, wild-type enzyme G39E
additional information
-
additional information
-
-
-
additional information
-
additional information
-
kinetics and substrate specificity of wild-type and mutant enzymes, overview
-
additional information
-
additional information
-
kinetics
-
additional information
-
additional information
A8WBX8, -
the recombinant enzyme shows an allosteric behaviour, overview
-
additional information
-
additional information
-
kinetics of wild-type and mutant enzymes
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.2
-
Ala-Pro
-
pH 7.8, 37C, recombinant His-tagged mutants F822A and Y844A
1
-
Ala-Pro
-
pH 7.8, 37C, recombinant His-tagged mutant V833A
8
-
Ala-Pro
-
pH 7.8, 37C, recombinant His-tagged mutant H859A
22
-
Ala-Pro
-
pH 7.8, 37C, recombinant His-tagged wild-type enzyme
683
-
Gly-Pro
-
-
55.3
-
Ile-Pro
-
-
109
-
L-Met-L-Pro
-
-
111
-
Leu-Pro
-
-
1079
-
Leu-Pro
O58691, -
pH 7.0, 70C, wild-type enzyme
1492
-
Leu-Pro
O58691, -
pH 7.0, 70C, mutant enzyme E127G/E252D
1660
-
Leu-Pro
O58691, -
pH 7.0, 70C, mutant enzyme A195T/G306S
2129
-
Leu-Pro
O58691, -
pH 7.0, 70C, mutant enzyme E36V
2861
-
Leu-Pro
O58691, -
pH 7.0, 70C, mutant enzyme Y301C/K342N
115
-
Met-Pro
-
-
123
-
Met-Pro
-
pH 7.0, 35C, recombinant wild-type enzyme; pH 7.0, 35C, wild-type enzyme
167
-
Met-Pro
-
pH 7.0, 35C, mutant enzyme G39E; pH 7.0, 35C, recombinant mutant G39E
171
-
Met-Pro
-
pH 7.0, 35C, mutant enzyme R19G/K71E/S229T; pH 7.0, 35C, recombinant mutant R19G/K71E/S229T
173
-
Met-Pro
-
pH 7.0, 35C, mutant enzyme R19G/G39E/K71E/S229T; pH 7.0, 35C, recombinant mutant R19G/G39E/K71E/S229T
767
-
Met-Pro
-
pH 7.0, 70C, recombinant wild-type enzyme; pH 7.0, 70C, wild-type enzyme
1017
-
Met-Pro
-
pH 7.0, 70C, recombinant mutant G39E; pH 7.0, 70C, wild-type enzyme G39E
1217
-
Met-Pro
-
pH 7.0, 70C, mutant enzyme R19G/K71E/S229T; pH 7.0, 70C, recombinant mutant R19G/K71E/S229T
2104
-
Met-Pro
-
pH 7.0, 100C, recombinant wild-type enzyme; pH 7.0, 100C, wild-type enzyme
2416
-
Met-Pro
-
pH 7.0, 70C, mutant enzyme R19G/G39E/K71E/S229T; pH 7.0, 70C, recombinant mutant R19G/G39E/K71E/S229T
2617
-
Met-Pro
O58885, O59565, P81535, -
pH 7.0, 100C
3812
-
Met-Pro
O58885, O59565, P81535, -
pH 7.0, 100C
4594
-
Met-Pro
-
pH 7.0, 100C, wild-type enzyme G39E
6396
-
Met-Pro
-
pH 7.0, 100C, mutant enzyme R19G/K71E/S229T; pH 7.0, 100C, recombinant mutant R19G/K71E/S229T
6995
-
Met-Pro
-
pH 7.0, 100C, recombinant mutant G39E
7481
-
Met-Pro
-
pH 7.0, 100C, mutant enzyme R19G/G39E/K71E/S229T; pH 7.0, 100C, recombinant mutant R19G/G39E/K71E/S229T
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
980
-
Leu-Pro
O58691, -
pH 7.0, 70C, mutant enzyme Y301C/K342N
21765
1172
-
Leu-Pro
O58691, -
pH 7.0, 70C, wild-type enzyme
21765
1331
-
Leu-Pro
O58691, -
pH 7.0, 70C, mutant enzyme E36V
21765
1522
-
Leu-Pro
O58691, -
pH 7.0, 70C, mutant enzyme E127G/E252D
21765
2049
-
Leu-Pro
O58691, -
pH 7.0, 70C, mutant enzyme A195T/G306S
21765
13
-
Met-Pro
-
pH 7.0, 35C, mutant enzyme G39E; pH 7.0, 35C, recombinant mutant G39E
21921
15
-
Met-Pro
-
pH 7.0, 35C, mutant enzyme R19G/K71E/S229T; pH 7.0, 35C, recombinant mutant R19G/K71E/S229T
21921
19
-
Met-Pro
-
pH 7.0, 35C, recombinant wild-type enzyme; pH 7.0, 35C, wild-type enzyme
21921
22
-
Met-Pro
-
pH 7.0, 35C, mutant enzyme R19G/G39E/K71E/S229T; pH 7.0, 35C, recombinant mutant R19G/G39E/K71E/S229T
21921
132
-
Met-Pro
-
pH 7.0, 70C, mutant enzyme R19G/K71E/S229T; pH 7.0, 70C, recombinant mutant R19G/K71E/S229T
21921
135
-
Met-Pro
-
pH 7.0, 70C, recombinant wild-type enzyme; pH 7.0, 70C, wild-type enzyme
21921
150
-
Met-Pro
-
pH 7.0, 70C, recombinant mutant G39E; pH 7.0, 70C, wild-type enzyme G39E
21921
266
-
Met-Pro
-
pH 7.0, 100C, recombinant wild-type enzyme; pH 7.0, 100C, wild-type enzyme
21921
317
-
Met-Pro
-
pH 7.0, 100C, recombinant mutant G39E; pH 7.0, 100C, wild-type enzyme G39E
21921
322
-
Met-Pro
-
pH 7.0, 70C, mutant enzyme R19G/G39E/K71E/S229T; pH 7.0, 70C, recombinant mutant R19G/G39E/K71E/S229T
21921
467
-
Met-Pro
-
pH 7.0, 100C, mutant enzyme R19G/K71E/S229T; pH 7.0, 100C, recombinant mutant R19G/K71E/S229T
21921
674
-
Met-Pro
-
pH 7.0, 100C, mutant enzyme R19G/G39E/K71E/S229T; pH 7.0, 100C, recombinant mutant R19G/G39E/K71E/S229T
21921
768
-
Met-Pro
O58885, O59565, P81535, -
pH 7.0, 100C
21921
2006
-
Met-Pro
O58885, O59565, P81535, -
pH 7.0, 100C
21921
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.05
-
Captopril
-
isozyme PD I, pH 7.8, 37C
0.038
-
carmustine
-
in 0.05 M Tris-HCl, pH 7.8, 2 mM MnCl2, at 37C
0.005
-
N-Benzyloxycarbonyl-L-proline
-
isozyme PD I, pH 7.8, 37C
0.082
-
N-[N'-(2-bromoethyl)-N'-nitrosocarbamoyl]-L-proline
-
in 0.05 M Tris-HCl, pH 7.8, 2 mM MnCl2, at 37C
0.005
-
netilmicin
-
-
0.05
-
Ni2+
-
isozyme PD II, pH 7.8, 37C
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.9e-07
-
-
substrate prophalan-L
0.024
-
-
PepX, cell extract
0.041
-
-
PepQ, cell extract
0.129
-
-
PepI, cell extract
0.33
-
-
mutant enzyme S307R, in the presence of 1 mM ZnCl2, using L-Lys-L-Pro as substrate, at 50C
0.48
-
-
mutant enzyme S307D, in the presence of 1 mM ZnCl2, using L-Lys-L-Pro as substrate, at 50C
0.64
-
-
mutant enzyme R293S, in the presence of 1 mM MnCl2, using L-Phe-L-Pro as substrate, at 50C
0.67
-
-
mutant H284A, pH 7.0, 100C
0.73
-
-
mutant H284L, pH 7.0, 100C
1.02
-
-
mutant D209A, pH 7.0, 100C
1.1
-
-
mutant enzyme S307D, in the presence of 1 mM ZnCl2, using L-Val-L-Pro as substrate, at 50C
1.4
-
-
mutant enzyme R293S, in the presence of 1 mM ZnCl2, using L-Phe-L-Pro as substrate, at 50C; mutant enzyme S307D, in the presence of 1 mM MnCl2, using L-Lys-L-Pro as substrate, at 50C
1.7
-
-
mutant enzyme S307D, in the presence of 1 mM ZnCl2, using L-Phe-L-Pro as substrate, at 50C
2
-
-
mutant enzyme R293S, in the presence of 1 mM MnCl2, using L-Lys-L-Pro as substrate, at 50C
2.7
-
-
mutant enzyme S307D, in the presence of 1 mM ZnCl2, using L-Arg-L-Pro as substrate, at 50C
3
3.9
-
mutant enzyme R293S/S307G, in the presence of 1 mM MnCl2, using L-Val-L-Pro as substrate, at 50C
3.2
-
-
mutant enzyme R293S, in the presence of 1 mM ZnCl2, using L-Lys-L-Pro as substrate, at 50C; mutant enzyme S307D, in the presence of 1 mM MnCl2, using L-Phe-L-Pro as substrate, at 50C
4.3
-
-
mutant enzyme R293S, in the presence of 1 mM ZnCl2, using L-Arg-L-Pro as substrate, at 50C
4.4
-
-
mutant enzyme S307G, in the presence of 1 mM ZnCl2, using L-Lys-L-Pro as substrate, at 50C
4.8
-
-
mutant enzyme R293S, in the presence of 1 mM ZnCl2, using L-Val-L-Pro as substrate, at 50C
5
-
-
mutant enzyme R293S, in the presence of 1 mM MnCl2, using L-Val-L-Pro as substrate, at 50C
5.2
-
-
mutant enzyme S307D, in the presence of 1 mM MnCl2, using L-Val-L-Pro as substrate, at 50C
5.3
-
-
mutant enzyme R293S, in the presence of 1 mM MnCl2, using L-Leu-L-Pro as substrate, at 50C
5.632
-
-
37C, pH 7.8, dipeptidase activity
5.9
-
-
mutant enzyme R293S, in the presence of 1 mM MnCl2, using L-Arg-L-Pro as substrate, at 50C
6.2
-
-
mutant enzyme S307R, in the presence of 1 mM MnCl2, using L-Phe-L-Pro as substrate, at 50C
7
-
-
mutant enzyme R293S/S307G, in the presence of 1 mM ZnCl2, using L-Phe-L-Pro as substrate, at 50C
7.8
-
-
mutant enzyme S307G, in the presence of 1 mM ZnCl2, using L-Arg-L-Pro as substrate, at 50C
8.2
-
-
mutant enzyme S307R, in the presence of 1 mM ZnCl2, using L-Arg-L-Pro as substrate, at 50C
8.9
-
-
mutant enzyme S307R, in the presence of 1 mM MnCl2, using L-Lys-L-Pro as substrate, at 50C
9.6
-
-
mutant enzyme S307G, in the presence of 1 mM MnCl2, using L-Lys-L-Pro as substrate, at 50C; mutant enzyme S307G, in the presence of 1 mM MnCl2, using L-Phe-L-Pro as substrate, at 50C
10
-
-
at 30C, with organophosphorus compound substrate diisopropyl phosphorofluoridate, DFP
10.6
-
-
mutant enzyme S307R, in the presence of 1 mM ZnCl2, using L-Val-L-Pro as substrate, at 50C
11.6
-
-
mutant enzyme S307D, in the presence of 1 mM MnCl2, using L-Arg-L-Pro as substrate, at 50C
11.9
-
-
mutant enzyme S307R, in the presence of 1 mM ZnCl2, using L-Phe-L-Pro as substrate, at 50C
12.4
-
-
mutant enzyme S307G, in the presence of 1 mM ZnCl2, using L-Phe-L-Pro as substrate, at 50C
12.8
-
-
mutant enzyme S307G, in the presence of 1 mM ZnCl2, using L-Val-L-Pro as substrate, at 50C
13.3
-
P12955
prolidase in presence of 10 mM Zn2+
13.4
-
-
mutant enzyme R293S/S307G, in the presence of 1 mM MnCl2, using L-Phe-L-Pro as substrate, at 50C
13.6
-
-
mutant enzyme R293S/S307G, in the presence of 1 mM ZnCl2, using L-Lys-L-Pro as substrate, at 50C
18.4
-
-
mutant enzyme S307R, in the presence of 1 mM MnCl2, using L-Val-L-Pro as substrate, at 50C
22.7
-
-
mutant enzyme R293S/S307G, in the presence of 1 mM MnCl2, using L-Leu-L-Pro as substrate, at 50C
25.6
-
-
mutant enzyme S307D, in the presence of 1 mM MnCl2, using L-Leu-L-Pro as substrate, at 50C
27.3
-
-
wild type enzyme, in the presence of 1 mM MnCl2, using L-Lys-L-Pro as substrate, at 50C
27.6
-
-
mutant enzyme R293S/S307G, in the presence of 1 mM MnCl2, using L-Lys-L-Pro as substrate, at 50C
30
-
-
at 55C, with organophosphorus compound substrate diisopropyl phosphorofluoridate, DFP
30.9
-
-
wild type enzyme, in the presence of 1 mM ZnCl2, using L-Lys-L-Pro as substrate, at 50C
31.5
-
-
mutant enzyme S307D, in the presence of 1 mM ZnCl2, using L-Leu-L-Pro as substrate, at 50C
32.3
-
-
mutant enzyme R293S/S307G, in the presence of 1 mM ZnCl2, using L-Arg-L-Pro as substrate, at 50C
32.7
-
-
mutant enzyme S307G, in the presence of 1 mM MnCl2, using L-Val-L-Pro as substrate, at 50C
36.9
-
-
mutant enzyme S307G, in the presence of 1 mM MnCl2, using L-Leu-L-Pro as substrate, at 50C
42.3
-
-
mutant enzyme S307R, in the presence of 1 mM MnCl2, using L-Arg-L-Pro as substrate, at 50C
46.7
-
-
mutant enzyme R293S/S307G, in the presence of 1 mM ZnCl2, using L-Val-L-Pro as substrate, at 50C
48.3
-
-
mutant enzyme R293S/S307G, in the presence of 1 mM MnCl2, using L-Arg-L-Pro as substrate, at 50C
49.47
-
-
-
53.7
-
-
mutant enzyme S307G, in the presence of 1 mM MnCl2, using L-Arg-L-Pro as substrate, at 50C
56.2
-
-
wild type enzyme, in the presence of 1 mM ZnCl2, using L-Arg-L-Pro as substrate, at 50C
64.9
-
-
mutant enzyme R293S, in the presence of 1 mM ZnCl2, using L-Leu-L-Pro as substrate, at 50C
67.7
-
-
wild type enzyme, in the presence of 1 mM ZnCl2, using L-Val-L-Pro as substrate, at 50C
78.2
-
-
mutant enzyme R293S/S307G, in the presence of 1 mM ZnCl2, using L-Leu-L-Pro as substrate, at 50C
81.8
-
-
mutant enzyme S307G, in the presence of 1 mM ZnCl2, using L-Leu-L-Pro as substrate, at 50C
87.8
-
-
mutant enzyme S307R, in the presence of 1 mM ZnCl2, using L-Leu-L-Pro as substrate, at 50C
100.8
-
-
mutant enzyme S307R, in the presence of 1 mM MnCl2, using L-Leu-L-Pro as substrate, at 50C
111.4
-
-
wild type enzyme, in the presence of 1 mM ZnCl2, using L-Phe-L-Pro as substrate, at 50C
158.3
-
P12955
prolidase in presence of 10 mM Mn2+
159.7
-
-
wild type enzyme, in the presence of 1 mM MnCl2, using L-Val-L-Pro as substrate, at 50C
166.1
-
-
wild type enzyme, in the presence of 1 mM MnCl2, using L-Phe-L-Pro as substrate, at 50C
197.2
-
A8WBX8, -
purified recombinant enzyme
223
-
-
-
226.5
-
-
cell lystae supernatant, pH 7.8, 37C
234.5
-
-
wild type enzyme, in the presence of 1 mM MnCl2, using L-Leu-L-Pro as substrate, at 50C
463.7
-
-
wild type enzyme, in the presence of 1 mM MnCl2, using L-Arg-L-Pro as substrate, at 50C
468.7
-
-
wild type enzyme, in the presence of 1 mM ZnCl2, using L-Leu-L-Pro as substrate, at 50C
590
-
-
purified crystallized recombinant enzyme
630
-
-
native enzyme
809
-
O58691, -
substratwe: Leu-Pro, pH 7.0, 70C, wild-type enzyme
1119
-
O58691, -
substrate: Leu-Pro, pH 7.0, 70C, mutant enzyme E127G/E252D
1245
-
O58691, -
substrate: Leu-Pro, pH 7.0, 70C, mutant enzyme A195T/G306S
1300
-
-
purified noncrystallized recombinant enzyme
1360
-
-
recombinant enzyme
1388
-
-
wild-type, pH 7.0, 100C
1597
-
O58691, -
substrate: Leu-Pro, pH 7.0, 70C, mutant enzyme E36V
1938
-
O58885, O59565, P81535, -
purified recombinant enzyme, 100C, substrate Met-Pro
1950
-
-
-
2000
-
-
-
2146
-
O58691, -
substrate: Leu-Pro, pH 7.0, 70C, mutant enzyme Y301C/K342N
2355
-
O58885, O59565, P81535, -
purified recombinant enzyme, 100C, substrate Met-Pro
21500
-
-
pH 7.8, 37C
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
serum prolidase is 952 U/l in patients with pleural tuberculosis
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
-
-
specific activities with melphalan and prodrugs in cancer cell lines, overview
additional information
-
-
activities of strain JD6.5 enzyme in the presence or absence of various biodegradeable and water-soluble wetting agents, degreasers, or foams, overview
additional information
-
O58885, O59565, P81535, -
substrate and metal specificities, recombinant enzyme, overview; substrate and metal specificities, recombinant enzyme, overview
additional information
-
-
overall tissue-specific prolidase activity in brain regions with different substrates
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
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5
-
-
dipeptidase activity, 20% of maximum activity
6
-
-
assay at
6.5
-
-
wild-type enzyme
6.8
-
-
substrate Ala-Pro
7
-
-
substrate Met-Pro
7
-
-
assay at
7
-
A8WBX8, -
recombinant enzyme
7
-
-
with Co2+ and substrate Met-Pro
7
-
O58885, O59565, P81535, -
two peaks at pH 5.0 and pH 7.0; two peaks at pH 5.0 and pH 7.0
7
-
-
assay at; assay at
7
-
-
assay at
7
-
O58691, -
assay at
7.25
7.5
-
prolidase I
7.4
-
-
substrate Gly-Pro
7.4
-
-
assay at
7.5
8
-
prolidase II
7.6
9
-
Tris-HCl buffer
7.6
-
-
assay at
7.8
8
-
assay at
7.8
-
-
assay at
7.8
-
-
-
7.8
-
-
assay at
7.8
-
-
-
7.8
-
-
assay at
7.8
-
-
assay at
7.8
-
P12955
assay at
8
-
-
-
8
-
-
dipeptidase activity
10
-
-
dipeptidase activity, 80% of maximum activity
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4
10
O58885, O59565, P81535, -
activity profile, overview; activity profile, overview
4
8.5
-
activity profiles of wild-type and mutant enzymes, overview
5
7.5
-
-
5.5
8.6
-
less than 10% activity below and above
6
8
A8WBX8, -
pH profile, overview
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
10
100
-
activities of wild-type and mutant enzymes at 100C
37
50
-
native enzyme
37
-
-
assay at
40
-
-
-
40
-
-
assay at
50
-
-
dipeptidase activity, sharp decrease in activity above
50
-
-
recombinant enzyme
50
-
-
-
50
-
A8WBX8, -
assay at
50
-
-
temperature optimum of the wild-type enzyme
50
-
P12955
assay at
60
-
-
temperature optimum of the mutant enzymes L193R, V302D, and L193T
70
-
-
temperature optimum of the mutant enzymes L193E/V302D and L193R/V302D, the wild-type enzyme is inactive
80
100
O58885, O59565, P81535, -
assay at; assay at
100
-
-
substrate Met-Pro
100
-
-
assay at
100
-
-
with Co2+ and substrate Met-Pro
100
-
O58691, -
wild-type enzyme and mutant enzymes A195T/G306S, Y301C/K342N, E127G/E252D and E36V
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
35
100
-
highest activities of wild-type and mutant enzymes at 100C
35
60
A8WBX8, -
67% of maximal activity at 60C, no activity at 70C
37
50
-
50% of maximal activity at 37C
50
100
-
hardly active below 50C, optimal activity at 100C
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
from pregenancies with healthy fetusses and those with neural tube defect
Manually annotated by BRENDA team
-
enzyme activity is increased in aortic dilatation compared to controls
Manually annotated by BRENDA team
-
cord blood
Manually annotated by BRENDA team
-
prolidase activity in blood plasma is about 6% as great as in erythrocytes
Manually annotated by BRENDA team
-
isoenzymes PD I and PD II. PD II activity is highest in the hippocampus, followed by the cerebellum, cerebral cortex, caudatum, and the midbrain. Age-related alterations in PD I and PD II
Manually annotated by BRENDA team
-
breast cancer tissue shows high enzyme activity, reduced collagen content and decreased expression of beta1-integrins
Manually annotated by BRENDA team
-
increased prolidase activity in breast cancer tissue
Manually annotated by BRENDA team
-
growth condition study and role of dipeptides, proline- and glutamate-containing peptides may contribute to the adaptation of the organism to high salt through their intracellular hydrolysis and/or direct accumulation, overview
Manually annotated by BRENDA team
-
increased PSR activity in case of colitis
Manually annotated by BRENDA team
-
prolidase activity is increased in ovarian cancer, overview
Manually annotated by BRENDA team
-
enzyme from a normal human, a human with prolidase deficiency and her mother
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
high activity
Manually annotated by BRENDA team
-
derived from normal skin and teloid tissue
Manually annotated by BRENDA team
-
derived from skin
Manually annotated by BRENDA team
-
isozymes PD I and PD II, high expression level of isozyme PD I, which is predominantly concentrated in renal cortex, where its activity is 2fold higher than in renal medulla
Manually annotated by BRENDA team
-
high activity
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
-
prolidase is down-regulated in lymphoma samples
Manually annotated by BRENDA team
-
higher expression of prolidase in tumor cells and particularly in melanoma cells
Manually annotated by BRENDA team
-
high enzyme expression level
Manually annotated by BRENDA team
-
high expression level
Manually annotated by BRENDA team
-
fibroblast cell line
Manually annotated by BRENDA team
-
inverse relationship of serum and placental levels of prolidase activity
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
inverse relationship of serum and placental levels of prolidase activity
Manually annotated by BRENDA team
-
enzyme activity is increased in patients with nonalcoholic steatohepatitis, NASH, compared to controls; serum prolidase enzyme activity is significantly higher in patients with non-alcoholic steatohepatitis than controls
Manually annotated by BRENDA team
-
normal skin and teloid tissue
Manually annotated by BRENDA team
-
high expression level of isozyme PD I
Manually annotated by BRENDA team
-
vaginal fluid
Manually annotated by BRENDA team
additional information
-
prolidase is especially active in growing tissues
Manually annotated by BRENDA team
additional information
-
organ distribution and developmental changes of isozymes PD I and PD II, overview
Manually annotated by BRENDA team
additional information
-
optimal growth at 100C
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
O58885, O59565, P81535, -
;
Manually annotated by BRENDA team
Lactococcus lactis subsp. cremoris AM2
-
-
-
Manually annotated by BRENDA team
Pyrococcus horikoshii 700860D-5
-
;
-
Manually annotated by BRENDA team
-
post-Golgi vesicular fraction
Manually annotated by BRENDA team
-
PD I is completely cytosolic, while PD II also occurs in the particulate fraction
Manually annotated by BRENDA team
-
dipeptidase function
Manually annotated by BRENDA team
additional information
-
subscellular localization in cells natively expressing the enzyme and in cells recombinantly expressing the enzyme
-
Manually annotated by BRENDA team
additional information
-
PD II is cytosolic and also occurs in the particulate fraction
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Pyrococcus furiosus (strain ATCC 43587 / DSM 3638 / JCM 8422 / Vc1)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)
Streptococcus pyogenes serotype M28 (strain MGAS6180)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
41000
-
-
gel filtration
43000
-
-
gel filtration
56000
-
-
native enzyme, SDS-PAGE
56000
-
-
SDS-PAGE
68000
70000
-
gel filtration
80000
-
A8WBX8, -
about, recombinant enzyme, gel filtration
100000
-
-
gel filtration
100000
-
-
gel filtration
108000
116000
-
gel filtration
108000
116000
-
gel filtration
108000
116000
-
gel filtration
108000
116000
-
gel filtration, prolidase I from normal human and mother of patient with prolidase deficiency
115000
-
-
gel filtration
120000
130000
-
gel filtration
120000
-
-
gel filtration
123000
-
-
recombinant enzyme from Escherichia coli
132000
-
-
gradient gel electrophoresis
165000
-
-
gel filtration, prolidase II
185000
-
-
gel filtration, prolidase II from normal human and mother of patient with prolidase deficiencyr
210000
-
-
analytical ultracentrifugation
440000
-
-
gel filtration
additional information
-
-
hydrodynamic properties of wild-type and mutant DPP8s
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 58000, processed glycoslyated enzyme, SDS-PAGE, x * 53000, unprocessed enzyme, SDS-PAGE
?
-
x * 56000, SDS-PAGE
?
-
x * 42000, SDS-PAGE
?
-
x * 73000, SDS-PAGE
?
-
x * 58000, recombinant enzyme, SDS-PAGE
?
O58885, O59565, P81535, -
x * 40000, recombinant enzyme, SDS-PAGE; x * 40000, recombinant enzyme, SDS-PAGE
?
Pyrococcus horikoshii 700860D-5
-
x * 40000, recombinant enzyme, SDS-PAGE; x * 40000, recombinant enzyme, SDS-PAGE
-
dimer
-
2 * 54305, calculation from DNA sequence
dimer
-
2 * 53000-58000, SDS-PAGE
dimer
-
1 * 64000 + 1 * 68000, SDS-PAGE
dimer
-
2 * 53000-58000, SDS-PAGE
dimer
-
2 * 50000, SDS-PAGE
dimer
-
2 * 53000-58000, SDS-PAGE
dimer
-
2 * 51000, SDS-PAGE
dimer
-
2 * 56000, SDS-PAGE, prolidase I from normal human and mother of patient with prolidase deficiencyr; 2 * 95000, SDS-PAGE, prolidase II from normal human and patient's mother
dimer
-
2 * 42000, SDS-PAGE
dimer
-
crystal structure
dimer
-
crystal structure, 2 subunits each with 2 domains, with the C-terminal domain bearing the active site
dimer
-
2 * 58000
dimer
-
2 * 58000, homodimerization via leucine zipper motif is required for activity, the active site is not required for dimerization
dimer
-
2 * 105000, recombinant His-tagged enzyme, SDS-PAGE
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
dimer
-
crystal structure analysis, active site analysis, overview
dimer
A8WBX8, -
2 * 40000, recombinant enzyme, SDS-PAGE, 2 * 40164, mass spectrometry
dimer
P12955
structure comparison to the enzyme from Pyrococcus horikoshii OT3 prolidase, overview
dimer
Lactococcus lactis NRRL B-1821
-
2 * 40000, recombinant enzyme, SDS-PAGE, 2 * 40164, mass spectrometry
-
homodimer
-
2 * 39400, structure-function relationship, overview. The enzyme shows a pita-bread fold that encompasses a highly conserved metal center and substrate-binding pocket that is located in the enzyme's C-terminal domain
homodimer
-
-
monomer
-
1 * 41000, SDS-PAGE
multimer
-
x * 40000, SDS-PAGE
oligomer
-
x * 58000, SDS-PAGE
monomer
Alteromonas sp. JD6.5, Lactobacillus casei IFPL 731
-
-
-
additional information
-
enzyme contains a leucine zipper motif
additional information
-
hydrodynamic properties of wild-type and mutant DPP8s, overview
additional information
-
crystal structure and active site organization, overview
additional information
-
molecular modeling
additional information
A8WBX8, -
molecular modeling, overview
additional information
-
The OPAA structure is composed of two domains, amino and carboxy domains, with the latter exhibiting a pita bread architecture and harboring the active site with the binuclear Mn2+ ions
additional information
-
The OPAA structure is composed of two domains, amino and carboxy domains, with the latter exhibiting a pita bread architecture and harboring the active site with the binuclear Mn2+ ions
-
additional information
Lactococcus lactis NRRL B-1821
-
molecular modeling, overview
-
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
glycoprotein
-
-
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
-
phosphorylation at a tyrosine residue activates the enzyme
phosphoprotein
-
enzyme phosphorylation on serine/threonine residue activating the enzyme; 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
proteolytic modification
-
a 29 amino acid signal or propeptide is cleaved from the enzyme after synthesis
phosphoprotein
-
increased enzymic activity after treatment with NO donors is accompanied by increase in serine/threonine phosphorylation of enzyme. 8-Br-cGMP strongly and rapidly stimulates enzyme activity by phosphorylation
side-chain modification
-
glycoprotein, 0.5% carbohydrate
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
purified enzyme, hanging drop method, mixing of 0.002 ml of protein solution containing 10 mg/ml protein in 1 mM 2-mercaptoethanol, 0.1 mM MnCl2, and 10 mM Tris-HCl, pH 7.2, with 0.002 ml of reservoir solution containing 16% PEG 4000, 20 mM MnCl2, 1 mM 2-mercaptoethanol, 270 mM ammonium acetate, and 60 mM sodium acetate, pH 4.6, at 20C, 2-4 days, X-ray diffraction structure determination and analysis
-
0.0025 ml of purified recombinant enzyme, 10 mg/ml, in 50 mM Tris-HCl, pH 8.5, 6.5-7.5% PEG 8000, 0.1 M magnesium acetate, hanging drop vapour diffusion, against 1.0 ml reservoir solution containing 13-15% PEG 8000, 0.2 M magnesium acetate, 50 mM Tris-HCl, pH 8.5, 20C, 180 days, addition of solid (2S,3R)-3-amino-2-hydroxy-5-methyl-hexanoyl-proline and 15% 2-methyl-2,4-pentanediol for formation and crystallization of enzyme-inhibitor complex, X-ray structure determination and analysis at 2.0 A resolution of crystal form II; native enzyme and in complex with inhibitor (2S,3R)-3-amino-2-hydroxy-5-methylhexanoyl-proline. One homodimer per asymmetric unit. Each subunit has two domains, the C-terminal domain includes the catalytic site centered on a dinuclear metal cluster
-
10 mg/ml purified recombinant enzyme in 0.25 M MOPS, pH 7.0, hanging drop vapour diffusion method, 0.0025 ml with equal volume of precipitant solution containing PEG 8000 or PEG 4000, best in 0.1 M Tris-HCl, pH 8.5, 0.2 M magnesium acetate, 13-15% PEG 8000, room temperature, after 1 day cyrstals of form I appear, after 6 months crystals of form II appear, X-ray structure determination and analysis at 3.2 A and 1.95 A resolution for Form I and II, respectively, cryoprotection with solution containing 2-methyl-2,4-pentanediol
-
enzyme with bound Zn2+ substituting Co2+
-
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5
9
-
-
6
8.5
-
for 60 min at 37C
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
30
55
A8WBX8, -
30 min, purified recombinant enzyme, over 50% remaining activity
37
-
-
slow inactivation in absence of Mn2+
40
-
-
inactivation above
48
-
-
abnormal prolidase, inactivation above
50
-
-
inactivation above
50
-
-
little activity remaining after 6 h
60
-
A8WBX8, -
30 min, purified recombinant enzyme, 22% remaining activity
67
-
A8WBX8, -
denaturation temperature
70
-
A8WBX8, -
30 min, purified recombinant enzyme, inactivation
80
-
-
loss of 50% activity after 6 h
90
-
O58885, O59565, P81535, -
purified recombinant enzyme, t1/2 is 21.5 h; purified recombinant enzyme, t1/2 is 21 h
90
-
-
mutants K71E/S229T and R19G/G39E/K71E/S229T loose 50% activity after 4 and 3 h, respectively, whereas mutant G39E does not show this loss of activity until 14 h, and the wild-type enzyme retains 50% activity after 21 h; R19G/K71E/S229T loses 50% of its activity after 4 h, R19G/G39E/K71E/S229T loses 50% of its activity after 3 h, G39E loses 50% of its activity after 14 h, wild-type enzyme loses 50% of its activity after 21 h
100
-
-
native Pfprol shows no loss of activity after incubation for 12 h at 100C, while the recombinant prolidase produced in Escherichia coli exhibits a 50% loss of activity after incubation for 6 h at 100C
100
-
O58885, O59565, P81535, -
purified recombinant enzyme, 8 h, 100% stable; purified recombinant enzyme, 8 h, 100% stable
112
-
O58691, -
Tm-value for mutant enzyme E127G/E252D is 112.2C
114
-
O58691, -
Tm-value for wild-type enzyme is 114.3C, Tm-value for mutant enzyme A195T/G306S is 114.4C, Tm-value for mutant enzyme Y301C/K342N is 113.8C
115
-
O58691, -
Tm-value for mutant enzyme E36V is 112.2C
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
Mn2+ and GSH stabilize the untagged recombinant enzyme
-
PEG and glycerol stabilize the enzyme
-
instable during purification
-
glutathione, stabilization
-
PEGylated prolidase is more stable than the native enzyme, PEGylated prolidase keeps about 41% of its initial activity up to 48 h while the native enzyme becomes completely inactive
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
4C, 1 week, 74% activity
-
37C, purified recombinant enzyme, loss of almost all activity after 2 days, 70% remaining activity after one day for the detagged enyzme, 47% remaining activity for the tagged enzyme
-
37C, recombinant enzyme from expression in Escherichia coli, stable for 6 days
-
-20C, 0.02 M Tris-HCl, pH 7.0, 4.0 mg/ml protein, at least 1 month
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant enzyme
-
2 isoenzymes
-
from JURKAT cells
-
partially; prolidase I and II
-
prolidase I and II
-
recombinant enzyme, expression in Saccharomyces cerevisiae
-
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
-
to homogeneity
-
DEAE Sephacel column chromatography
-
recombinant strain NRRL B-1821 enzyme 11.8fold from Escherichia coli by ammonium sulfate fractionation and anion exchange chromatography, method optimization
A8WBX8, -
native and recombinant form
-
recombinant wild-type and mutant enzymes from Escherichia coli strain JD1 (lambdaDE3) by heat treatment at 80C for 30 min, hydrophobic interaction chromatography, and anion exchange chromatography
-
recombinant wild-type enzyme and mutant enzymes A195T/G306S, Y301C/K342N, E127G/E252D and E36V
O58691, -
native isozymes partially from kidney by anion exchange chromatography
-
separation of native isozymes PD I and PD II from brain homogenate by gel filtration
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
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 in Escherichia coli
-
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-etrminally His-tagged enzyme in Escherichia coli strain BL21
P12955
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
-
expression in Escherichia coli
-
expressed in Escherichia coli Top10F' cells
-
expression of the enzyme from strain NRRL B-1821 in Escherichia coli, method optimization
A8WBX8, -
DNA and amino acid sequence determination and analysis, expression of wild-type and mutant enzymes in Escherichia coli strain JD1 (lambdaDE3)
-
DNA and amino acid sequence determination and anaylsis
-
expression in Escherichia coli
-
expression in Escherichia coli
O58691, -
gene PH0974, DNA and amino acid sequence determination and analysis, expression in Escherichia coli strain BL21 (lambdaDE3); gene PH1149, DNA and amino acid sequence determination and analysis, expression in Escherichia coli strain BL21 (lambdaDE3); gene PH1902, DNA and amino acid sequence determination and analysis
O58885, O59565, P81535, -
expressed in CHO-C9 cells
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
A212P
-
naturally occuring mutation involved in prolidase deficiency
F822A
-
site-directed mutagenesis, the mutant enzyme shows reduced activity compared to the wild-type enzyme
G278D
-
naturally occuring point mutation causing prolidase deficiency
G448R
-
naturally occuring point mutation causing prolidase deficiency
H859A
-
site-directed mutagenesis, the mutant enzyme shows reduced activity compared to the wild-type enzyme
R184Q
-
naturally occuring point mutation causing prolidase deficiency
R265X
-
naturally occuring point mutation causing prolidase deficiency
R276N
-
naturally occuring point mutation causing prolidase deficiency
S202F
-
naturally occuring point mutation causing prolidase deficiency
S202F
-
naturally occuring mutation involved in prolidase deficiency
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
H303S/S307G
-
inactive
L193E
-
site-directed mutagenesis, the mutant is active on Pro-Pro in contrast to the wild-type enzyme, the mutant shows altered substrate specificity and temperature profile compared to the wild-type enzyme
L193E/V302D
-
site-directed mutagenesis, the mutant shows altered substrate specificity and temperature profile compared to the wild-type enzyme
L193R
-
site-directed mutagenesis, the mutation in the S1 site eliminates the allosteric behaviour of the enzyme, the mutant is active on Pro-Pro and Gly-Pro in presence of zinc ions in contrast to the wild-type enzyme, the mutant shows altered substrate specificity and temperature profile compared to the wild-type enzyme
L193R/V302D
-
site-directed mutagenesis, the mutant shows altered substrate specificity and temperature profile compared to the wild-type enzyme
L193T
-
site-directed mutagenesis, the mutant is active on Pro-Pro and Gly-Pro in contrast to the wild-type enzyme, the mutant shows altered substrate specificity and temperature profile compared to the wild-type enzyme
R293S
-
the mutation results in the disappearance of the allosteric behaviour yielding a Hill constant of 0.98 while the wild type has a constant of 1.58 and suppresses the substrate inhibition that is observed in other mutants and wild type enzyme, the Km value for L-Leu-L-Pro is 2.9fold larger and Vmax is approximately 50% less as compared to the wild type enzyme
R293S/S307G
-
mutant shows strongly reduced specific activity towards L-Leu-L-Pro compared to the wild type enzyme
S307D
-
mutant shows reduced specific activity towards L-Leu-L-Pro compared to the wild type enzyme
S307G
-
mutant shows reduced specific activity towards L-Leu-L-Pro compared to the wild type enzyme
S307R
-
mutant shows reduced specific activity towards L-Leu-L-Pro compared to the wild type enzyme
V302D
-
site-directed mutagenesis, the mutation in the S1 site eliminates the allosteric behaviour of the enzyme. The mutant is active on Pro-Pro in presence of zinc ions in contrast to the wild-type enzyme, the mutant shows altered substrate specificity and temperature profile compared to the wild-type enzyme
V302K
-
site-directed mutagenesis, the mutant shows altered substrate specificity and temperature profile compared to the wild-type enzyme
V302T
-
site-directed mutagenesis, the mutant shows altered substrate specificity and temperature profile compared to the wild-type enzyme
D209A
-
less than 0.1% enzymic activity, contains 0.7 Co per subunit, maximal activity with 0.5 mM Co2+, less than 20% residual activity with 10 mM Co2+
E313L
-
protein is highly misfolded, remains aggregated and recalcitrant during purification
E327L
-
no enzymic activity, contains 0.03 Co per sunbunit
G39E
-
at 35C, 70C and 100C the mutant exhibits higher Vmax and kcat values than wild-type prolidase for Met-Pro. kcat/Km for Met-Pro is 70% of wild-type value at 35C, kcat/Km for Met-Pro is 80% of wild-type value at 70C, kcat/Km for Met-Pro is 1.2fold higher than wild-type value at 100C. Relative specific activity towards Met-Pro at 100C is 103% of wild-type activity. Relative specific activity towards Leu-Pro at 100C is 85% of wild-type activity. Relative specific activity towards Phe-Pro at 100C is 60% of wild-type activity. Relative specific activity towards Ala-Pro at 100C is 35% of wild-type activity. Relative specific activity towards Gly-Pro at 100C is 37% of wild-type activity. Relative specific activity towards Arg-Pro at 100C is 132% of wild-type activity. Catalytic activity of the mutant enzyme has similar response to changes in pH as wild-type enzyme and shows optimal activity at pH 6.0, although the activity is 60% of wild-type activity; site-directed mutagenesis, the mutant shows altered kinetics and temperature profile
H284A
-
less than 0.1% enzymic activity, protein is unfolded
R19G/G39E/K71E/S229T
-
mutant enzyme shows a higher activity than wild-type enzyme over a broad range of temperatures, the thermostability of the mutant enzymes is less compared to wild type. At 35C, 70C and 100C the mutant exhibits higher Vmax and kcat values than wild-type prolidase for Met-Pro. kcat/Km for Met-Pro is 1.2fold higher than wild-type value at 35C, kcat/Km for Met -Pro is 1.8fold higher than wild-type value at 70C, kcat/Km for Met-Pro is 2.5fold higher than wild-type value at 100C. Relative specific activity towards Met-Pro at 100C is 143% of wild-type activity. Relative specific activity towards Leu-Pro at 100C is 79% of wild-type activity. Relative specific activity towards Phe-Pro at 100C is 122% of wild-type activity. Relative specific activity towards Ala-Pro at 100C is 38% of wild-type activity. Relative specific activity towards Gly-Pro at 100C is 10% of wild-type activity. Relative specific activity towards Arg-Pro at 100C is 112% of wild-type activity; site-directed mutagenesis, the mutant shows altered kinetics and temperature profile
R19G/K71E/S229
-
site-directed mutagenesis, the mutant shows altered kinetics and temperature profile
R19G/K71E/S229T
-
mutant enzyme shows a higher activity than wild-type enzyme over a broad range of temperatures, the thermostability of the mutant enzymes is less compared to wild type. At 35C, 70C and 100C the mutant exhibits higher Vmax and kcat values than wild-type prolidase for Met-Pro. kcat/Km for Met-Pro is 1.1fold higher than wild-type value at 35C, kcat/Km for Met -Pro comparable to wild-type value at 70C, kcat/Km for Met-Pro is 2.4fold higher than wild-type value at 100C. Relative specific activity towards Met-Pro at 100C is 137% of wild-type activity. Relative specific activity towards Leu-Pro at 100C is 169% of wild-type activity. Relative specific activity towards Phe-Pro at 100C is 97% of wild-type activity. Relative specific activity towards Ala-Pro at 100C is 95% of wild-type activity. Relative specific activity towards Gly-Pro at 100C is 47% of wild-type activity. Relative specific activity towards Arg-Pro at 100C is 101% of wild-type activity. Catalytic activity of the mutant enzyme has similar response to changes in pH as wild-type enzyme and shows optimal activity at pH 7.0, although the activity is 89% of wild-type activity
A195T/G306S
O58691, -
mutation causes an increase in Tm-value of 0.1C. Mutation causes an 1.7fold increase of the catalytic efficiency towards Leu-Pro
E127G/E252D
O58691, -
mutation causes an decrease in Tm-value of 2.1C. Mutation causes an 1.3fold increase of the catalytic efficiency towards Leu-Pro
Y301C/K342N
O58691, -
mutation causes an decrease in Tm-value of 0.5C. Mutation causes an 1.2fold decrease of the catalytic efficiency towards Leu-Pro
A195T/G306S
Pyrococcus horikoshii DSM 12428
-
mutation causes an increase in Tm-value of 0.1C. Mutation causes an 1.7fold increase of the catalytic efficiency towards Leu-Pro
-
E127G/E252D
Pyrococcus horikoshii DSM 12428
-
mutation causes an decrease in Tm-value of 2.1C. Mutation causes an 1.3fold increase of the catalytic efficiency towards Leu-Pro
-
Y301C/K342N
Pyrococcus horikoshii DSM 12428
-
mutation causes an decrease in Tm-value of 0.5C. Mutation causes an 1.2fold decrease of the catalytic efficiency towards Leu-Pro
-
L368R
-
naturally occuring mutation involved in prolidase deficiency
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
H284L
-
less than 0.1% enzymic activity, contains 0.28 Co per subunit. Inhibitory effect of high Co2+-concentration is less pronounced than in wild-type
additional information
-
the use of Pyrococcus furiosus prolidase for organophosphorus nerve agent decontamination is restricted by the fact that this enzyme displays a narrow functional temperature range. Like many other enzymes isolated from hyperthermophiles, Pyrococcus furiosus prolidase has only 50% activity at 80C and displays little activity at temperatures below 50C. Therefore a random-mutated Pyrococcus furiosus prolidase gene library is constructed and screened for production of mutants with increased activity at room temperature while maintaining thermostability. The mutant enzyme shows increased activity over the pH range of 57. At pH 5.0, the mutant activity is 1.6fold higher than wild-type activity, and at pH 7.0, it is 1.2fold higher than wild type
E36V
O58691, -
mutation causes an increase in Tm-value of 0.6C. Mutation causes an 1.1fold increase of the catalytic efficiency towards Leu-Pro
additional information
O58691, -
randomly mutated enzymes are prepared Tt obtain a better enzyme for organophosphorus nerve agent decontamination and to investigate the structural factors that may influence protein thermostability and thermoactivity
E36V
Pyrococcus horikoshii DSM 12428
-
mutation causes an increase in Tm-value of 0.6C. Mutation causes an 1.1fold increase of the catalytic efficiency towards Leu-Pro
-
additional information
Pyrococcus horikoshii DSM 12428
-
randomly mutated enzymes are prepared Tt obtain a better enzyme for organophosphorus nerve agent decontamination and to investigate the structural factors that may influence protein thermostability and thermoactivity
-
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
degradation
-
advantages of using Alteromonas recombinant prolidase in biodecontamination foams due to its high activity against G-type nerve agents, such as soman and sarin
degradation
-
advantages of using Alteromonas recombinant prolidase in biodecontamination foams due to its high activity against G-type nerve agents, such as soman and sarin
-
diagnostics
-
prolidase might be a useful marker for the diagnosis of lymphoma
diagnostics
-
cord blood prolidase activity may be a good indicator of fetal maturation and gestational age
diagnostics
-
prolidase is a potential biomarker for melanoma, and the enzyme is a target for drug development in cancer therapy
diagnostics
-
prolidase is a marker of collagen turnover
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
drug development
-
the enzyme is used as target enzyme for specific melanoma prodrug activation
drug development
-
the enzyme is a target in breast cancer therapy
drug development
-
prolidase is a potential biomarker for melanoma, and the enzyme is a target for drug development in cancer therapy
food industry
-
prolidase can be used in dietary industry as bitterness reducing agent
medicine
-
enzyme is a possible target for doxycyclin-induced inhibition of collagen synthesis in the treatment of osteoarthritis
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
-
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
-
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
-
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
-
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
-
the presence of atrial fibrillation in patients with severe mitral stenosis may be associated with the plasma prolidase activity
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 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
-
prolidase-loaded chitosan nanoparticles permit to restore prolidase activity in prolidase deficiency fibroblasts for 8 days
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
-
Recombinant human prolidase is used for enzyme replacement therapy in prolidase deficiency
food industry
-
prolidases are employed in the cheese-ripening process to improve cheese taste and texture
food industry
Lactobacillus casei IFPL 731
-
prolidases are employed in the cheese-ripening process to improve cheese taste and texture
-
food industry
-
prolidases are employed in the cheese-ripening process to improve cheese taste and texture
analysis
-
applications using prolidase to detoxify organophosphorous compounds nerve agents include its incorporation into fire-fighting foams and as biosensors for organophosphorous compound detection
biotechnology
-
the enzyme is of particular interest because it can be used in many biotechnological applications
degradation
-
prolidase is able to degrade toxic organophosphorus compounds, namely, by cleaving the P-F and P-O bonds in the nerve agents, sarin and soman. Applications using prolidase to detoxify organophosphorous nerve agents include its incorporation into fire-fighting foams and as biosensors for organophosphorous compound detection
food industry
-
prolidases are employed in the cheese-ripening process to improve cheese taste and texture