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Literature summary for 3.4.21.26 extracted from

  • Garcia-Horsman, J.A.; Maennistoe, P.T.; Venaelaeinen, J.I.
    On the role of prolyl oligopeptidase in health and disease (2007), Neuropeptides, 41, 1-24.
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
2-mercaptoethanol activation of the cytsolic isozyme, but not of the extracellular isozyme Homo sapiens
DTT activation of the cytsolic isozyme, but not of the extracellular isozyme Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
gene prep, mapping to chromosome 10B2-B3, DNA and amino acid sequence analysis, expression analysis Mus musculus
gene prep, mapping to chromosome 6q22, expression analysis Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
enzyme in complex with inhibitor benzyloxycarbonyl-Pro-Prolinal, X-ray diffraction structure determination at high resolution Sus scrofa

Protein Variants

Protein Variants Comment Organism
additional information a mutant deficient for the dpoA gene is resistant to the effects of lithium Flavobacterium sp.

Inhibitors

Inhibitors Comment Organism Structure
4-(2-aminoethyl)benzenesulfonyl fluoride inhibition of extracellular isozyme Homo sapiens
Aprotinin inhibition of extracellular isozyme Homo sapiens
benzyloxycarbonyl-Pro-prolinal i.e. Z-Pro-prolinal Dictyostelium discoideum
benzyloxycarbonyl-Pro-prolinal i.e. Z-Pro-prolinal Flavobacterium sp.
benzyloxycarbonyl-Pro-prolinal i.e. Z-Pro-Prolinal, inhibition of cytsolic isozyme, but no inhibition of the extracellular isozyme in serum Homo sapiens
benzyloxycarbonyl-Pro-prolinal i.e. Z-Pro-prolinal Mus musculus
benzyloxycarbonyl-Pro-prolinal i.e. Z-Pro-prolinal Novosphingobium capsulatum
benzyloxycarbonyl-Pro-prolinal i.e. Z-Pro-prolinal Rattus norvegicus
benzyloxycarbonyl-Pro-prolinal i.e. Z-Pro-prolinal Sus scrofa
JTP-4819
-
Dictyostelium discoideum
JTP-4819
-
Flavobacterium sp.
JTP-4819
-
Homo sapiens
JTP-4819
-
Mus musculus
JTP-4819
-
Novosphingobium capsulatum
JTP-4819
-
Rattus norvegicus
JTP-4819
-
Sus scrofa
additional information structure-function relationship of inhibitors, specificity at the P2 and S3 position, overview Dictyostelium discoideum
additional information structure-function relationship of inhibitors, specificity at the P2 and S3 position, overview Flavobacterium sp.
additional information structure-function relationship of inhibitors, specificity at the P2 and S3 position, overview Homo sapiens
additional information structure-function relationship of inhibitors, specificity at the P2 and S3 position, overview Mus musculus
additional information structure-function relationship of inhibitors, specificity at the P2 and S3 position, overview Novosphingobium capsulatum
additional information structure-function relationship of inhibitors, specificity at the P2 and S3 position, overview Rattus norvegicus
additional information structure-function relationship of inhibitors, specificity at the P2 and S3 position, overview Sus scrofa
ONO-1603
-
Dictyostelium discoideum
ONO-1603
-
Flavobacterium sp.
ONO-1603
-
Homo sapiens
ONO-1603
-
Mus musculus
ONO-1603
-
Novosphingobium capsulatum
ONO-1603
-
Rattus norvegicus
ONO-1603
-
Sus scrofa
S-17092
-
Dictyostelium discoideum
S-17092
-
Flavobacterium sp.
S-17092
-
Homo sapiens
S-17092
-
Mus musculus
S-17092
-
Novosphingobium capsulatum
S-17092
-
Rattus norvegicus
S-17092
-
Sus scrofa
SUAM-1221
-
Dictyostelium discoideum
SUAM-1221
-
Flavobacterium sp.
SUAM-1221
-
Homo sapiens
SUAM-1221
-
Mus musculus
SUAM-1221
-
Novosphingobium capsulatum
SUAM-1221
-
Rattus norvegicus
SUAM-1221
-
Sus scrofa

Localization

Localization Comment Organism GeneOntology No. Textmining
cytoplasm
-
Mus musculus 5737
-
cytosol
-
Homo sapiens 5829
-
cytosol
-
Rattus norvegicus 5829
-
extracellular
-
Homo sapiens
-
-
extracellular
-
Dictyostelium discoideum
-
-
extracellular
-
Flavobacterium sp.
-
-
extracellular
-
Novosphingobium capsulatum
-
-
membrane
-
Dictyostelium discoideum 16020
-
membrane
-
Flavobacterium sp. 16020
-
membrane
-
Novosphingobium capsulatum 16020
-
membrane isoyzme in brain synaptosome membranes Rattus norvegicus 16020
-
synaptosome
-
Rattus norvegicus
-
-

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
80000
-
x * 80000, about Mus musculus
87000
-
x * 87000, extracellular isozyme, SDS-PAGE Homo sapiens
170000
-
cytosolic isozyme Homo sapiens
174000
-
extracellular isozyme Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
alpha-melanocyte-stimulating hormone + H2O Mus musculus
-
?
-
?
alpha-melanocyte-stimulating hormone + H2O Homo sapiens
-
?
-
?
alpha-melanocyte-stimulating hormone + H2O Rattus norvegicus
-
?
-
?
alpha-melanocyte-stimulating hormone + H2O Sus scrofa
-
?
-
?
angiotensin I + H2O Mus musculus
-
?
-
?
angiotensin I + H2O Homo sapiens
-
?
-
?
angiotensin I + H2O Rattus norvegicus
-
?
-
?
angiotensin I + H2O Sus scrofa
-
?
-
?
angiotensin II + H2O Mus musculus
-
?
-
?
angiotensin II + H2O Homo sapiens
-
?
-
?
angiotensin II + H2O Rattus norvegicus
-
?
-
?
angiotensin II + H2O Sus scrofa
-
?
-
?
arginine-vasopressin + H2O Mus musculus
-
?
-
?
arginine-vasopressin + H2O Homo sapiens
-
?
-
?
arginine-vasopressin + H2O Rattus norvegicus
-
?
-
?
arginine-vasopressin + H2O Sus scrofa
-
?
-
?
beta-endorphin + H2O Mus musculus
-
?
-
?
beta-endorphin + H2O Homo sapiens
-
?
-
?
beta-endorphin + H2O Rattus norvegicus
-
?
-
?
beta-endorphin + H2O Sus scrofa
-
?
-
?
bradykinin + H2O Mus musculus
-
?
-
?
bradykinin + H2O Homo sapiens
-
?
-
?
bradykinin + H2O Rattus norvegicus
-
?
-
?
bradykinin + H2O Sus scrofa
-
?
-
?
gonadotropin releasing hormone + H2O Mus musculus
-
?
-
?
gonadotropin releasing hormone + H2O Homo sapiens
-
?
-
?
gonadotropin releasing hormone + H2O Rattus norvegicus
-
?
-
?
gonadotropin releasing hormone + H2O Sus scrofa
-
?
-
?
additional information Novosphingobium capsulatum enzyme regulation, overview ?
-
?
additional information Dictyostelium discoideum enzyme inhibition leads to inhibition of lithium effects, the loss of enzyme activity evokes a 4fold increase in the inositol-3-phosphate concentration counteracting the Li+ ions, enzyme regulation, overview ?
-
?
additional information Homo sapiens the enzyme is a serine protease, that digests small peptide-like hormones, neuroactive peptides, and various cellular factors, it is implicated in several biological processes and diseases, e.g. in some psychiatric disorders, most probably through interference in the inositol cycle, it is important in the metabolism of substance P, arginine vasopressin, thyroliberin, and gonadoliberin, enzyme regulation probably involving gluten, prep expression is downregulated in coelic disease patients in complete remission, overview ?
-
?
additional information Mus musculus the enzyme is a serine protease, that digests small peptide-like hormones, neuroactive peptides, and various cellular factors, it is implicated in several biological processes and diseases, e.g. in some psychiatric disorders, most probably through interference in the inositol cycle, it is important in the metabolism of substance P, arginine vasopressin, thyroliberin, and gonadoliberin, enzyme regulation, overview ?
-
?
additional information Rattus norvegicus the enzyme is a serine protease, that digests small peptide-like hormones, neuroactive peptides, and various cellular factors, it is implicated in several biological processes and diseases, e.g. in some psychiatric disorders, most probably through interference in the inositol cycle, it is important in the metabolism of substance P, arginine vasopressin, thyroliberin, and gonadoliberin, enzyme regulation, overview ?
-
?
additional information Sus scrofa the enzyme is a serine protease, that digests small peptide-like hormones, neuroactive peptides, and various cellular factors, it is implicated in several biological processes and diseases, e.g. in some psychiatric disorders, most probably through interference in the inositol cycle, it is important in the metabolism of substance P, arginine vasopressin, thyroliberin, and gonadoliberin, enzyme regulation, overview ?
-
?
additional information Flavobacterium sp. the enzyme removes most of the gut-digestion-resistant gliadin peptides in the host gut luman of coeliac disease patients, overview, enzyme regulation, overview ?
-
?
neurotensin + H2O Mus musculus
-
?
-
?
neurotensin + H2O Homo sapiens
-
?
-
?
neurotensin + H2O Rattus norvegicus
-
?
-
?
neurotensin + H2O Sus scrofa
-
?
-
?
oxytoxin + H2O Mus musculus
-
?
-
?
oxytoxin + H2O Homo sapiens
-
?
-
?
oxytoxin + H2O Rattus norvegicus
-
?
-
?
oxytoxin + H2O Sus scrofa
-
?
-
?
Substance P + H2O Mus musculus
-
?
-
?
Substance P + H2O Homo sapiens
-
?
-
?
Substance P + H2O Rattus norvegicus
-
?
-
?
Substance P + H2O Sus scrofa
-
?
-
?
thyrotropin releasing hormone + H2O Mus musculus
-
?
-
?
thyrotropin releasing hormone + H2O Homo sapiens
-
?
-
?
thyrotropin releasing hormone + H2O Rattus norvegicus
-
?
-
?
thyrotropin releasing hormone + H2O Sus scrofa
-
?
-
?

Organism

Organism UniProt Comment Textmining
Dictyostelium discoideum
-
-
-
Flavobacterium sp.
-
-
-
Homo sapiens
-
gene prep
-
Mus musculus
-
gene prep
-
Novosphingobium capsulatum
-
-
-
Rattus norvegicus
-
-
-
Sus scrofa P23687
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
no modification
-
Mus musculus
no modification
-
Homo sapiens
no modification
-
Rattus norvegicus
no modification
-
Sus scrofa

Purification (Commentary)

Purification (Comment) Organism
extracellular isozyme, cytsolic isozyme, overview Homo sapiens

Reaction

Reaction Comment Organism Reaction ID
Hydrolysis of --Pro-/- and to a lesser extent --Ala-/- in oligopeptides catalytic mechanism, structure-function relationship Mus musculus
Hydrolysis of --Pro-/- and to a lesser extent --Ala-/- in oligopeptides catalytic mechanism, structure-function relationship Homo sapiens
Hydrolysis of --Pro-/- and to a lesser extent --Ala-/- in oligopeptides catalytic mechanism, structure-function relationship Rattus norvegicus
Hydrolysis of --Pro-/- and to a lesser extent --Ala-/- in oligopeptides catalytic mechanism, structure-function relationship Dictyostelium discoideum
Hydrolysis of --Pro-/- and to a lesser extent --Ala-/- in oligopeptides catalytic mechanism, structure-function relationship Flavobacterium sp.
Hydrolysis of --Pro-/- and to a lesser extent --Ala-/- in oligopeptides catalytic mechanism, structure-function relationship Sus scrofa
Hydrolysis of --Pro-/- and to a lesser extent --Ala-/- in oligopeptides catalytic mechanism, structure-function relationship, the substrate induces an opening at the interface pf the peptidase and the beta-propeller domains while entering into the active site, concerted movements of the domains are required for enzyme activity Novosphingobium capsulatum

Source Tissue

Source Tissue Comment Organism Textmining
amygdala
-
Mus musculus
-
amygdala
-
Homo sapiens
-
amygdala
-
Rattus norvegicus
-
blood
-
Homo sapiens
-
brain
-
Mus musculus
-
brain high enzyme content Rattus norvegicus
-
brain cortex
-
Mus musculus
-
brain cortex
-
Homo sapiens
-
brain cortex
-
Rattus norvegicus
-
central nervous system distribution, overview Mus musculus
-
central nervous system distribution, overview Homo sapiens
-
central nervous system distribution, overview Rattus norvegicus
-
cerebellum
-
Mus musculus
-
cerebellum
-
Homo sapiens
-
cerebellum
-
Rattus norvegicus
-
endothelial cell
-
Homo sapiens
-
epithelial cell
-
Homo sapiens
-
fibroblast
-
Homo sapiens
-
heart
-
Homo sapiens
-
heart
-
Rattus norvegicus
-
hippocampus
-
Mus musculus
-
hippocampus
-
Homo sapiens
-
hippocampus
-
Rattus norvegicus
-
hypothalamus
-
Mus musculus
-
hypothalamus
-
Homo sapiens
-
hypothalamus
-
Rattus norvegicus
-
kidney
-
Rattus norvegicus
-
liver
-
Rattus norvegicus
-
lung
-
Homo sapiens
-
lung
-
Rattus norvegicus
-
lung cancer cell high enzyme content Homo sapiens
-
lymphocyte
-
Homo sapiens
-
pituitary gland
-
Rattus norvegicus
-
platelet
-
Homo sapiens
-
prostate cancer cell high enzyme content Homo sapiens
-
prostate fluid
-
Homo sapiens
-
rectum
-
Homo sapiens
-
renal cortex
-
Homo sapiens
-
seminal fluid
-
Homo sapiens
-
spleen
-
Homo sapiens
-
spleen
-
Rattus norvegicus
-
striatum
-
Mus musculus
-
striatum
-
Homo sapiens
-
striatum
-
Rattus norvegicus
-
testis
-
Homo sapiens
-
uterus
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
alpha-melanocyte-stimulating hormone + H2O
-
Mus musculus ?
-
?
alpha-melanocyte-stimulating hormone + H2O
-
Homo sapiens ?
-
?
alpha-melanocyte-stimulating hormone + H2O
-
Rattus norvegicus ?
-
?
alpha-melanocyte-stimulating hormone + H2O
-
Sus scrofa ?
-
?
angiotensin I + H2O
-
Mus musculus ?
-
?
angiotensin I + H2O
-
Homo sapiens ?
-
?
angiotensin I + H2O
-
Rattus norvegicus ?
-
?
angiotensin I + H2O
-
Sus scrofa ?
-
?
angiotensin II + H2O
-
Mus musculus ?
-
?
angiotensin II + H2O
-
Homo sapiens ?
-
?
angiotensin II + H2O
-
Rattus norvegicus ?
-
?
angiotensin II + H2O
-
Sus scrofa ?
-
?
arginine-vasopressin + H2O
-
Mus musculus ?
-
?
arginine-vasopressin + H2O
-
Homo sapiens ?
-
?
arginine-vasopressin + H2O
-
Rattus norvegicus ?
-
?
arginine-vasopressin + H2O
-
Sus scrofa ?
-
?
beta-endorphin + H2O
-
Mus musculus ?
-
?
beta-endorphin + H2O
-
Homo sapiens ?
-
?
beta-endorphin + H2O
-
Rattus norvegicus ?
-
?
beta-endorphin + H2O
-
Sus scrofa ?
-
?
bradykinin + H2O
-
Mus musculus ?
-
?
bradykinin + H2O
-
Homo sapiens ?
-
?
bradykinin + H2O
-
Rattus norvegicus ?
-
?
bradykinin + H2O
-
Sus scrofa ?
-
?
gonadotropin releasing hormone + H2O
-
Mus musculus ?
-
?
gonadotropin releasing hormone + H2O
-
Homo sapiens ?
-
?
gonadotropin releasing hormone + H2O
-
Rattus norvegicus ?
-
?
gonadotropin releasing hormone + H2O
-
Sus scrofa ?
-
?
additional information enzyme regulation, overview Novosphingobium capsulatum ?
-
?
additional information enzyme inhibition leads to inhibition of lithium effects, the loss of enzyme activity evokes a 4fold increase in the inositol-3-phosphate concentration counteracting the Li+ ions, enzyme regulation, overview Dictyostelium discoideum ?
-
?
additional information the enzyme is a serine protease, that digests small peptide-like hormones, neuroactive peptides, and various cellular factors, it is implicated in several biological processes and diseases, e.g. in some psychiatric disorders, most probably through interference in the inositol cycle, it is important in the metabolism of substance P, arginine vasopressin, thyroliberin, and gonadoliberin, enzyme regulation probably involving gluten, prep expression is downregulated in coelic disease patients in complete remission, overview Homo sapiens ?
-
?
additional information the enzyme is a serine protease, that digests small peptide-like hormones, neuroactive peptides, and various cellular factors, it is implicated in several biological processes and diseases, e.g. in some psychiatric disorders, most probably through interference in the inositol cycle, it is important in the metabolism of substance P, arginine vasopressin, thyroliberin, and gonadoliberin, enzyme regulation, overview Mus musculus ?
-
?
additional information the enzyme is a serine protease, that digests small peptide-like hormones, neuroactive peptides, and various cellular factors, it is implicated in several biological processes and diseases, e.g. in some psychiatric disorders, most probably through interference in the inositol cycle, it is important in the metabolism of substance P, arginine vasopressin, thyroliberin, and gonadoliberin, enzyme regulation, overview Rattus norvegicus ?
-
?
additional information the enzyme is a serine protease, that digests small peptide-like hormones, neuroactive peptides, and various cellular factors, it is implicated in several biological processes and diseases, e.g. in some psychiatric disorders, most probably through interference in the inositol cycle, it is important in the metabolism of substance P, arginine vasopressin, thyroliberin, and gonadoliberin, enzyme regulation, overview Sus scrofa ?
-
?
additional information the enzyme removes most of the gut-digestion-resistant gliadin peptides in the host gut luman of coeliac disease patients, overview, enzyme regulation, overview Flavobacterium sp. ?
-
?
additional information substrate specificity, overview, the enzyme cleaves at the C-terminal side of proline residues and more slowly of alanine residues, no activity with large proteins with over 30 amino acids Mus musculus ?
-
?
additional information substrate specificity, overview, the enzyme cleaves at the C-terminal side of proline residues and more slowly of alanine residues, no activity with large proteins with over 30 amino acids Homo sapiens ?
-
?
additional information substrate specificity, overview, the enzyme cleaves at the C-terminal side of proline residues and more slowly of alanine residues, no activity with large proteins with over 30 amino acids Rattus norvegicus ?
-
?
additional information substrate specificity, overview, the enzyme cleaves at the C-terminal side of proline residues and more slowly of alanine residues, no activity with large proteins with over 30 amino acids Sus scrofa ?
-
?
additional information the enzyme cleaves at the C-terminal side of proline residues, the bacterial enzyme is also capable of cleaving Ala-Xaa and Val-Xaa bonds, no activity with large proteins with over 30 amino acids Flavobacterium sp. ?
-
?
additional information the enzyme cleaves at the C-terminal side of proline residues, the bacterial enzyme is also capable of cleaving Ala-Xaa and Val-Xaa bonds, no activity with large proteins with over 30 amino acids Novosphingobium capsulatum ?
-
?
neurotensin + H2O
-
Mus musculus ?
-
?
neurotensin + H2O
-
Homo sapiens ?
-
?
neurotensin + H2O
-
Rattus norvegicus ?
-
?
neurotensin + H2O
-
Sus scrofa ?
-
?
oxytoxin + H2O
-
Mus musculus ?
-
?
oxytoxin + H2O
-
Homo sapiens ?
-
?
oxytoxin + H2O
-
Rattus norvegicus ?
-
?
oxytoxin + H2O
-
Sus scrofa ?
-
?
Substance P + H2O
-
Mus musculus ?
-
?
Substance P + H2O
-
Homo sapiens ?
-
?
Substance P + H2O
-
Rattus norvegicus ?
-
?
Substance P + H2O
-
Sus scrofa ?
-
?
thyrotropin releasing hormone + H2O
-
Mus musculus ?
-
?
thyrotropin releasing hormone + H2O
-
Homo sapiens ?
-
?
thyrotropin releasing hormone + H2O
-
Rattus norvegicus ?
-
?
thyrotropin releasing hormone + H2O
-
Sus scrofa ?
-
?

Subunits

Subunits Comment Organism
? x * 80000, about Mus musculus
? x * 87000, extracellular isozyme, SDS-PAGE Homo sapiens
More the enzyme structure contains two domains, the peptidase domain consitst of N- and C-terminal residues 1-72 and 428-710 containing the catalytic triad Ser554, Asp641, and His680 and is arranged in a classical alpha/beta hydrolase fold, the seven-bladed beta-propeller domain, residues 73-427, is radially arranged around the central tunnel embedded within the cylinder, where the narrow active site is located Sus scrofa

Synonyms

Synonyms Comment Organism
POP
-
Mus musculus
POP
-
Homo sapiens
POP
-
Rattus norvegicus
POP
-
Dictyostelium discoideum
POP
-
Flavobacterium sp.
POP
-
Novosphingobium capsulatum
POP
-
Sus scrofa
post-proline cleaving enzyme
-
Homo sapiens
post-proline endopeptidase
-
Homo sapiens
PPCE
-
Homo sapiens
prolyl endopeptidase
-
Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.00000035
-
benzyloxycarbonyl-Pro-prolinal
-
Mus musculus
0.00000083
-
JTP-4819
-
Rattus norvegicus
0.0000015
-
S-17092
-
Homo sapiens
0.0000072
-
SUAM-1221
-
Rattus norvegicus
0.000012
-
ONO-1603
-
Rattus norvegicus