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Literature summary for 3.4.21.26 extracted from

  • Gass, J.; Khosla, C.
    Prolyl endopeptidases (2007), Cell. Mol. Life Sci., 64, 345-355.
    View publication on PubMed

Application

Application Comment Organism
drug development the enzyme is a pharmacological target for neurological diseases due to its high brain concentration and ability to cleave neuropeptides in vitro Homo sapiens
pharmacology microbial PEPs are studied as potential therapeutics for celiac sprue, an inflammatory disease of the small intestine triggered by proline-rich gluten Pyrococcus furiosus
pharmacology microbial PEPs are studied as potential therapeutics for celiac sprue, an inflammatory disease of the small intestine triggered by proline-rich gluten Myxococcus xanthus
pharmacology microbial PEPs are studied as potential therapeutics for celiac sprue, an inflammatory disease of the small intestine triggered by proline-rich gluten Elizabethkingia meningoseptica
pharmacology microbial PEPs are studied as potential therapeutics for celiac sprue, an inflammatory disease of the small intestine triggered by proline-rich gluten Novosphingobium capsulatum

Cloned(Commentary)

Cloned (Comment) Organism
individual expression of isolated peptidase domain and catalytic domain Sus scrofa

Protein Variants

Protein Variants Comment Organism
additional information by using directed evolution techniques, the thermostability of the enzyme from Flavobacterium meningosepticum is improved by 1200fold, measured at 60┬░C, the thermostable enzyme contains 12 individual mutations, many of which are located near the N and C termini of the enzyme Elizabethkingia meningoseptica
additional information kinetic analysis of selected enzyme mutants Myxococcus xanthus
additional information knockout mutation reverses the effect of the drugs, the mutants show elevated levels of multiple inositol polyphosphate phosphatase, MIPP, activity Dictyostelium discoideum

General Stability

General Stability Organism
the enzyme is quite stable to the pancreatic enzymes, trypsin, chymotrypsin, elastase, and carboxypeptidase A at pH 6.5 and 37┬░C for 60 min retaining more than 60% of its activity Elizabethkingia meningoseptica
the enzyme is quite stable to the pancreatic enzymes, trypsin, chymotrypsin, elastase, and carboxypeptidase A, at upt to 3 mg/ml, at pH 6.5 and 37┬░C for 60 min retaining more than 60% of its activity Myxococcus xanthus

Inhibitors

Inhibitors Comment Organism Structure
lithium reverses the effect of the drugs Dictyostelium discoideum
S 17092 selective enzyme inhibitor, pharmacodynamics and pharmacokinetics, overview Homo sapiens
S 17092 selective enzyme inhibitor, pharmacodynamics and pharmacokinetics, overview Mus musculus
S 17092 selective enzyme inhibitor, pharmacodynamics and pharmacokinetics, overview Rattus norvegicus
Valproic acid reverses the effect of the drugs Dictyostelium discoideum
Z-Pro-prolinal a transition state analog inhibitor, binding structure Myxococcus xanthus
Z-Pro-prolinal a transition state analog inhibitor, binding structure Novosphingobium capsulatum

Localization

Localization Comment Organism GeneOntology No. Textmining
cytosol
-
Homo sapiens 5829
-
cytosol
-
Rattus norvegicus 5829
-
additional information the highest levels in particulate fractions in the synaptosomal and the myelin fractions Rattus norvegicus
-
-
additional information the highest levels in particulate fractions in the synaptosomal and the myelin fractions with a a fibrillary, cytoskeleton-like distribution, the enzyme is co-localized with tubulin and is a binding partner of tubulin, overview Homo sapiens
-
-
perinuclear space
-
Homo sapiens
-
-
synaptosome
-
Homo sapiens
-
-
synaptosome
-
Rattus norvegicus
-
-

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
71000
-
x * 71000 Pyrococcus furiosus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
alpha-melanocyte-stimulating hormone + H2O Rattus norvegicus
-
?
-
?
arginine-vasopressin + H2O Mus musculus
-
?
-
?
arginine-vasopressin + H2O Homo sapiens
-
?
-
?
arginine-vasopressin + H2O Rattus norvegicus
-
?
-
?
arginine-vasopressin + H2O Sus scrofa
-
?
-
?
additional information Rattus norvegicus the enzyme is involved with the inactivation of regulatory neuropeptides ?
-
?
additional information Homo sapiens the enzyme is involved with the inactivation of regulatory neuropeptides, enzyme activity is correlated to an increase in protein secretion, suggesting that the enzyme may be involved in regulating secretory processes ?
-
?
Substance P + H2O Mus musculus
-
?
-
?
Substance P + H2O Homo sapiens
-
?
-
?
Substance P + H2O Rattus norvegicus
-
?
-
?
Substance P + H2O Sus scrofa
-
?
-
?

Organism

Organism UniProt Comment Textmining
Dictyostelium discoideum
-
-
-
Elizabethkingia meningoseptica
-
-
-
Homo sapiens
-
-
-
Mus musculus
-
-
-
Myxococcus xanthus
-
-
-
Novosphingobium capsulatum
-
-
-
Pyrococcus furiosus
-
-
-
Rattus norvegicus
-
-
-
Sus scrofa
-
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
proteolytic modification limited proteolysis of the porcine enzyme with trypsin reveals a cleavage site at the Lys196-Ser197 bond in the flexible loop region of the propeller domain that interacts with the catalytic domain Sus scrofa

Reaction

Reaction Comment Organism Reaction ID
Hydrolysis of --Pro-/- and to a lesser extent --Ala-/- in oligopeptides the catalytic triad Ser, Asp, His is located in a large cavity at the interface of the two domains, the serine residue is located on what is called a nucleophile elbow, at the tip of a very sharp turn, it is surrounded by several small residues that provide relatively little steric hindrance Mus musculus
Hydrolysis of --Pro-/- and to a lesser extent --Ala-/- in oligopeptides the catalytic triad Ser, Asp, His is located in a large cavity at the interface of the two domains, the serine residue is located on what is called a nucleophile elbow, at the tip of a very sharp turn, it is surrounded by several small residues that provide relatively little steric hindrance Homo sapiens
Hydrolysis of --Pro-/- and to a lesser extent --Ala-/- in oligopeptides the catalytic triad Ser, Asp, His is located in a large cavity at the interface of the two domains, the serine residue is located on what is called a nucleophile elbow, at the tip of a very sharp turn, it is surrounded by several small residues that provide relatively little steric hindrance Rattus norvegicus
Hydrolysis of --Pro-/- and to a lesser extent --Ala-/- in oligopeptides the catalytic triad Ser, Asp, His is located in a large cavity at the interface of the two domains, the serine residue is located on what is called a nucleophile elbow, at the tip of a very sharp turn, it is surrounded by several small residues that provide relatively little steric hindrance Sus scrofa
Hydrolysis of --Pro-/- and to a lesser extent --Ala-/- in oligopeptides the catalytic triad Ser, Asp, His is located in a large cavity at the interface of the two domains, the serine residue is located on what is called a nucleophile elbow, at the tip of a very sharp turn, it is surrounded by several small residues that provide relatively little steric hindrance Pyrococcus furiosus
Hydrolysis of --Pro-/- and to a lesser extent --Ala-/- in oligopeptides the catalytic triad Ser, Asp, His is located in a large cavity at the interface of the two domains, the serine residue is located on what is called a nucleophile elbow, at the tip of a very sharp turn, it is surrounded by several small residues that provide relatively little steric hindrance Dictyostelium discoideum
Hydrolysis of --Pro-/- and to a lesser extent --Ala-/- in oligopeptides the catalytic triad Ser, Asp, His is located in a large cavity at the interface of the two domains, the serine residue is located on what is called a nucleophile elbow, at the tip of a very sharp turn, it is surrounded by several small residues that provide relatively little steric hindrance Myxococcus xanthus
Hydrolysis of --Pro-/- and to a lesser extent --Ala-/- in oligopeptides the catalytic triad Ser, Asp, His is located in a large cavity at the interface of the two domains, the serine residue is located on what is called a nucleophile elbow, at the tip of a very sharp turn, it is surrounded by several small residues that provide relatively little steric hindrance Elizabethkingia meningoseptica
Hydrolysis of --Pro-/- and to a lesser extent --Ala-/- in oligopeptides the catalytic triad Ser, Asp, His is located in a large cavity at the interface of the two domains, the serine residue is located on what is called a nucleophile elbow, at the tip of a very sharp turn, it is surrounded by several small residues that provide relatively little steric hindrance Novosphingobium capsulatum

Source Tissue

Source Tissue Comment Organism Textmining
brain
-
Mus musculus
-
brain
-
Rattus norvegicus
-
brain
-
Sus scrofa
-
brain highest enzyme activity in the brain cortex, and lowest in the cerebellum Homo sapiens
-
brain cortex
-
Homo sapiens
-
central nervous system
-
Rattus norvegicus
-
cerebellum
-
Homo sapiens
-
cerebral cortex
-
Rattus norvegicus
-
glioma cell
-
Homo sapiens
-
HEK-293 cell
-
Homo sapiens
-
hippocampus
-
Rattus norvegicus
-
kidney
-
Mus musculus
-
kidney
-
Homo sapiens
-
kidney
-
Rattus norvegicus
-
kidney
-
Sus scrofa
-
liver
-
Mus musculus
-
liver
-
Homo sapiens
-
liver
-
Rattus norvegicus
-
liver
-
Sus scrofa
-
lung
-
Mus musculus
-
lung
-
Homo sapiens
-
lung
-
Rattus norvegicus
-
lung
-
Sus scrofa
-
medulla oblongata
-
Rattus norvegicus
-
additional information tissue distribution analysis Mus musculus
-
additional information tissue distribution analysis Rattus norvegicus
-
additional information tissue distribution analysis, no activity in the urine Homo sapiens
-
muscle
-
Mus musculus
-
muscle
-
Homo sapiens
-
muscle
-
Rattus norvegicus
-
muscle
-
Sus scrofa
-
neuroblastoma cell
-
Homo sapiens
-
pituitary gland
-
Rattus norvegicus
-
saliva
-
Homo sapiens
-
semen
-
Homo sapiens
-
serum
-
Homo sapiens
-
skeletal muscle
-
Mus musculus
-
skeletal muscle
-
Homo sapiens
-
skeletal muscle
-
Rattus norvegicus
-
skeletal muscle
-
Sus scrofa
-
submandibular gland
-
Mus musculus
-
submandibular gland
-
Homo sapiens
-
submandibular gland
-
Rattus norvegicus
-
submandibular gland
-
Sus scrofa
-
testis
-
Mus musculus
-
testis
-
Homo sapiens
-
testis
-
Rattus norvegicus
-
testis
-
Sus scrofa
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
alpha-melanocyte-stimulating hormone + H2O
-
Rattus norvegicus ?
-
?
arginine-vasopressin + H2O
-
Mus musculus ?
-
?
arginine-vasopressin + H2O
-
Homo sapiens ?
-
?
arginine-vasopressin + H2O
-
Rattus norvegicus ?
-
?
arginine-vasopressin + H2O
-
Sus scrofa ?
-
?
gluten + H2O
-
Myxococcus xanthus ?
-
?
gluten + H2O
-
Elizabethkingia meningoseptica ?
-
?
gluten + H2O
-
Novosphingobium capsulatum ?
-
?
additional information the enzyme is involved with the inactivation of regulatory neuropeptides Rattus norvegicus ?
-
?
additional information the enzyme is involved with the inactivation of regulatory neuropeptides, enzyme activity is correlated to an increase in protein secretion, suggesting that the enzyme may be involved in regulating secretory processes Homo sapiens ?
-
?
additional information substrate specificity, overview, the enzyme hydrolyzes the peptide bond on the carboxyl side of internal proline residues of oligopeptide substrates with up to 30 amino acids, the S2' subsite had the highest specificity of the S1'-S3' subsites, this subsite prefers Pro residues, followed by Leu, Met, Phe, and Ala residues, the S1' subsite has lower specificity than the S2', with the strongest preference for hydrophobic, e.g. Leu, and aromatic, e.g. Phe, residues, and the greatest discrimination against Pro residues Elizabethkingia meningoseptica ?
-
?
additional information the enzyme hydrolyzes the peptide bond on the carboxyl side of internal proline residues of oligopeptide substrates with up to 30 amino acids, substrate specificity, overview Mus musculus ?
-
?
additional information the enzyme hydrolyzes the peptide bond on the carboxyl side of internal proline residues of oligopeptide substrates with up to 30 amino acids, substrate specificity, overview Homo sapiens ?
-
?
additional information the enzyme hydrolyzes the peptide bond on the carboxyl side of internal proline residues of oligopeptide substrates with up to 30 amino acids, substrate specificity, overview Rattus norvegicus ?
-
?
additional information the enzyme hydrolyzes the peptide bond on the carboxyl side of internal proline residues of oligopeptide substrates with up to 30 amino acids, substrate specificity, overview Sus scrofa ?
-
?
additional information the enzyme hydrolyzes the peptide bond on the carboxyl side of internal proline residues of oligopeptide substrates with up to 30 amino acids, substrate specificity, overview Pyrococcus furiosus ?
-
?
additional information the enzyme hydrolyzes the peptide bond on the carboxyl side of internal proline residues of oligopeptide substrates with up to 30 amino acids, substrate specificity, overview Dictyostelium discoideum ?
-
?
additional information the enzyme hydrolyzes the peptide bond on the carboxyl side of internal proline residues of oligopeptide substrates with up to 30 amino acids, substrate specificity, overview Myxococcus xanthus ?
-
?
additional information the enzyme hydrolyzes the peptide bond on the carboxyl side of internal proline residues of oligopeptide substrates with up to 30 amino acids, substrate specificity, overview Novosphingobium capsulatum ?
-
?
N-carbobenzyloxy-Ala-Pro-2-naphthylamide + H2O
-
Mus musculus N-carbobenzyloxy-Ala-Pro + 2-naphthylamine
-
?
N-carbobenzyloxy-Ala-Pro-2-naphthylamide + H2O
-
Homo sapiens N-carbobenzyloxy-Ala-Pro + 2-naphthylamine
-
?
N-carbobenzyloxy-Ala-Pro-2-naphthylamide + H2O
-
Rattus norvegicus N-carbobenzyloxy-Ala-Pro + 2-naphthylamine
-
?
N-succinyl-glycyl-proline-4-methylcoumarin-7-amide + H2O
-
Mus musculus N-succinyl-glycyl-proline + 7-amino-4-methylcoumarin
-
?
N-succinyl-glycyl-proline-4-methylcoumarin-7-amide + H2O
-
Homo sapiens N-succinyl-glycyl-proline + 7-amino-4-methylcoumarin
-
?
N-succinyl-glycyl-proline-4-methylcoumarin-7-amide + H2O
-
Rattus norvegicus N-succinyl-glycyl-proline + 7-amino-4-methylcoumarin
-
?
Substance P + H2O
-
Mus musculus ?
-
?
Substance P + H2O
-
Homo sapiens ?
-
?
Substance P + H2O
-
Rattus norvegicus ?
-
?
Substance P + H2O
-
Sus scrofa ?
-
?

Subunits

Subunits Comment Organism
? x * 71000 Pyrococcus furiosus
More tertiary structure, overview, the enzyme has a two-domain structure whose unique seven-blade beta-propeller domain works with the catalytic domain, mechanism for peptide entry between the two domains, overview Myxococcus xanthus
More tertiary structure, overview, the enzyme has a two-domain structure whose unique seven-blade beta-propeller domain works with the catalytic domain, mechanism for peptide entry between the two domains, overview Novosphingobium capsulatum
More the enzyme has a two-domain structure whose unique seven-blade beta-propeller domain works with the catalytic domain, mechanism for peptide entry between the two domains, overview Mus musculus
More the enzyme has a two-domain structure whose unique seven-blade beta-propeller domain works with the catalytic domain, mechanism for peptide entry between the two domains, overview Homo sapiens
More the enzyme has a two-domain structure whose unique seven-blade beta-propeller domain works with the catalytic domain, mechanism for peptide entry between the two domains, overview Rattus norvegicus
More the enzyme has a two-domain structure whose unique seven-blade beta-propeller domain works with the catalytic domain, mechanism for peptide entry between the two domains, overview Pyrococcus furiosus
More the enzyme has a two-domain structure whose unique seven-blade beta-propeller domain works with the catalytic domain, mechanism for peptide entry between the two domains, overview Dictyostelium discoideum
More the enzyme has a two-domain structure whose unique seven-blade beta-propeller domain works with the catalytic domain, mechanism for peptide entry between the two domains, overview Elizabethkingia meningoseptica
More the enzyme has a two-domain structure whose unique seven-blade beta-propeller domain works with the catalytic domain, mechanism for peptide entry between the two domains, the flexible loop region of the propeller domain, residues 192-205, that interacts with the catalytic domain, has the highest flexibility within the enzyme, molecular dynamics analysis, overview Sus scrofa

Synonyms

Synonyms Comment Organism
POP
-
Mus musculus
POP
-
Homo sapiens
POP
-
Rattus norvegicus
POP
-
Sus scrofa
POP
-
Pyrococcus furiosus
POP
-
Dictyostelium discoideum
POP
-
Myxococcus xanthus
POP
-
Elizabethkingia meningoseptica
POP
-
Novosphingobium capsulatum

Temperature Optimum [┬░C]

Temperature Optimum [┬░C] Temperature Optimum Maximum [┬░C] Comment Organism
85 90
-
Pyrococcus furiosus

Temperature Stability [┬░C]

Temperature Stability Minimum [┬░C] Temperature Stability Maximum [┬░C] Comment Organism
4
-
24 h, stable Pyrococcus furiosus
37
-
24 h, stable Pyrococcus furiosus
85
-
overnight, remaining activity Pyrococcus furiosus

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.000001
-
S 17092 extracellular enzyme Homo sapiens
0.00003
-
S 17092 intracellular enzyme Homo sapiens