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3.4.24.15: thimet oligopeptidase

This is an abbreviated version!
For detailed information about thimet oligopeptidase, go to the full flat file.

Word Map on EC 3.4.24.15

Reaction

Preferential cleavage of bonds with hydrophobic residues at P1, P2 and P3' and a small residue at P1' in substrates of 5-15 residues =

Synonyms

BIE, bradykinin-inactivating endopeptidase, EC 3.4.22.19, EC 3.4.99.31, endo-oligopeptidase A, endooligopeptidase A, endopeptidase 24-15, endopeptidase 24.15, endopeptidase EC 3.4.24.15, EOPA, EP 24.15, EP24.15, MdpA, metallo-dipeptidase aeruginosa, metalloendopeptidase 24.15, metalloendopeptidase EC 3.4.24.15, metallopeptidase, More, MP78, neutral endopeptidase 24.15, PA4498, peptidase, thimet oligo-, Pz peptidase A, Pz peptidase B, Pz-peptidase, Pz-peptidase A, soluble metallo-endopeptidase, soluble metallopeptidase, thimet oligopeptidase, thimet peptidase, thimet-oligopeptidase, thiol-dependent metalloendopeptidase, THOP1, TOP, Top1, Top2

ECTree

     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.24 Metalloendopeptidases
                3.4.24.15 thimet oligopeptidase

Engineering

Engineering on EC 3.4.24.15 - thimet oligopeptidase

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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E469R/R498T
-
site-directed mutagenesis of the substrate recognition residues leads to a swap of substrate specificity from thimet oligopeptidase to neurolysin, EC 3.4.24.16, the mutant cleaves neurolysin sites, overview
H495N/E469R/R498T
-
site-directed mutagenesis of the substrate recognition residues leads to a swap of substrate specificity from thimet oligopeptidase to neurolysin, EC 3.4.24.16, the mutant cleaves neurolysin sites, overview
H600A
-
the mutation affects both Km and kcat, the mutant shows changes in the pH-profile, overview
M490R/E469R/R498T
-
site-directed mutagenesis of the substrate recognition residues leads to a swap of substrate specificity from thimet oligopeptidase to neurolysin, EC 3.4.24.16, the mutant cleaves neurolysin sites, overview
M490R/H495N/E469R
-
site-directed mutagenesis of the substrate recognition residues leads to a swap of substrate specificity from thimet oligopeptidase to neurolysin, EC 3.4.24.16, the mutant cleaves TOP and neurolysin sites, overview
M490R/H495N/R498T
-
site-directed mutagenesis of the substrate recognition residues leads to a swap of substrate specificity from thimet oligopeptidase to neurolysin, EC 3.4.24.16, the mutant cleaves TOP and neurolysin sites, overview
E502Q
-
inactive mutant enzyme
A607G
-
site-directed mutagenesis, the mutation does not affect the overall fold of the protein, the mutant shows altered substrate specificity and kinetics with fluorogenic peptide substrates compared to the wild-type enzyme
C246S/C248S/C253S
site-directed mutagenesis, the mutations abolish the DTT and H2O2 effects on rTOP activity. The triple-mutated rTOP is not affected by DTT
D159A
-
similar to wild-type regarding enzymatic activity, secondary structure, calcium sensitivity and immunoreactivity
D93A
-
similar to wild-type regarding enzymatic activity, secondary structure, calcium sensitivity and immunoreactivity. Reduced ability to associate with the plasma membrane
D93A/D153A
-
similar to wild-type regarding enzymatic activity, secondary structure, calcium sensitivity and immunoreactivity. Reduced ability to associate with the plasma membrane
E502A
-
complete loss of enzymatic activity
G599A
-
decrease in the activity towards the 7-methoxycoumarin-4-acetyl-Pro-Leu-Gly-Pro-Lys-dinitrophenol and 7-methoxycoumarin-Leu-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Lys(Dnp)-OH substrates, with little effect or in activity towards 7-methoxycoumarin-4-acetyl-[Ala7, Lys(dinitrophenol)9]-bradykinin
G603A
-
increase in preference for the five-residue 7-methoxycoumarin-4-acetyl-Pro-Leu-Gly-Pro-Lys-dinitrophenol substrate and, to a lesser extent, for the 10-residue 7-methoxycoumarin-Leu-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Lys(Dnp)-OH substrate
G603A/G604A
-
increase in preference for the five-residue 7-methoxycoumarin-4-acetyl-Pro-Leu-Gly-Pro-Lys-dinitrophenol substrate and, to a lesser extent, for the 10-residue 7-methoxycoumarin-Leu-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Lys(Dnp)-OH substrate
G603P
-
decrease in catalytic activity towards all substrates tested
G604A
-
decrease in the activity towards the 7-methoxycoumarin-4-acetyl-Pro-Leu-Gly-Pro-Lys-dinitrophenol and 7-methoxycoumarin-Leu-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Lys(Dnp)-OH substrates, with little effect or in activity towards 7-methoxycoumarin-4-acetyl-[Ala7, Lys(dinitrophenol)9]-bradykinin
G611A
-
decrease in the activity towards the 7-methoxycoumarin-4-acetyl-Pro-Leu-Gly-Pro-Lys-dinitrophenol and 7-methoxycoumarin-Leu-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Lys(Dnp)-OH substrates, with little effect or in activity towards 7-methoxycoumarin-4-acetyl-[Ala7, Lys(dinitrophenol)9]-bradykinin
H473A
-
complete loss of enzymatic activity
H474A
-
complete loss of enzymatic activity
H477A
-
complete loss of enzymatic activity
Y605A
-
site-directed mutagenesis, the mutation does not affect the overall fold of the protein, TOP Y605A is inhibited less efficiently by JA-2, the mutant shows altered substrate specificity and kinetics with fluorogenic peptide substrates compared to the wild-type enzyme
Y605F
Y605F/Y612F
-
marked decrease in catalytic activity, but neither Y605 nor Y612 is necessary for hydrolysis of 7-methoxycoumarin-4-acetyl-[Ala7, Lys(dinitrophenol)9]-bradykinin
Y612F
additional information