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Literature summary for 3.4.21.76 extracted from

  • Hinkofer, L.C.; Seidel, S.A.; Korkmaz, B.; Silva, F.; Hummel, A.M.; Braun, D.; Jenne, D.E.; Specks, U.
    A monoclonal antibody (MCPR3-7) interfering with the activity of proteinase 3 by an allosteric mechanism (2013), J. Biol. Chem., 288, 26635-26648.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.4.21.76

Application

Application Comment Organism
drug development proteinase 3-inhibiting antibodies may play a role in autoimmune vasculitis and can be exploited as highly selective inhibitors Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
expression of His-tagged wild-type enzyme, expression of C-terminally c-myc-tagged wild-type pro-enzyme and mature enzyme, and of the C-terminally c-myc-His tagged truncated active site mutant enzyme in HEK-293 cells Homo sapiens

Protein Variants

Protein Variants Comment Organism
S195A site-directed mutagenesis, cDNA construction of a catalytically inactive active site enzyme mutant lacking the codons for the N-terminal activation dipeptide, DELTAPR3ctp-S195A Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
Alpha1-proteinase inhibitor the inhibition is highly dependent on the proper conformation of an exposed reactive center loop, which serves as a pseudosubstrate. Inhibitor mutant E342K is less effective due to an altered conformation of the reactive center loop Homo sapiens
protein 3-specific MCPR3-7 antibody the monoclonal antibody interfers with the activity of proteinase 3 by an allosteric mechanism. It can change its conformation and impair interactions with alpha1-proteinase inhibitor. The conformation of the S1 pocket of the enzyme is not changed significantly after binding of MCPR3-7, but rather the S1' subsite of the enzyme is changed Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens P24158
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-

Posttranslational Modification

Posttranslational Modification Comment Organism
proteolytic modification the pro-enzyme zymogen has to be proteolytically activated Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
neutrophil enzyme expression on neutrophil membranes Homo sapiens
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promyelocyte
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 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
5-TAMRA-VADnVADYQ-DAP(CF) + H2O a fluorescence resonance energy transfer, FRET, substrate. The reaction is inhibited by antibody MCPR3-7 binding Homo sapiens ?
-
 ?
Abz-Tyr-Tyr-Abu-ANB-NH2 + H2O a fluorescence resonance energy transfer, FRET, substrate. The reaction is inhibited by antibody MCPR3-7 binding Homo sapiens ?
-
 ?
Ahx-PYFA-4-nitroanilide + H2O the reaction is inhibited by antibody MCPR3-7 binding Homo sapiens ?
-
 ?
Boc-Ala-ONp + H2O the reaction is not inhibited by antibody MCPR3-7 binding Homo sapiens ?
-
 ?
Boc-Ala-Pro-nVal-SBzl + H2O the reaction is not inhibited by antibody MCPR3-7 binding Homo sapiens ?
-
 ?
For-Ala-Ala-Pro-Abu-SBzl + H2O the reaction is partly inhibited by antibody MCPR3-7 binding Homo sapiens ?
-
 ?

Synonyms

Synonyms Comment Organism
PR3
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 Homo sapiens
proteinase 3
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 Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
 assay at Homo sapiens

General Information

General Information Comment Organism
additional information proteinase 3 is an abundant serine protease with high similarity to neutrophil elastase Homo sapiens
physiological function proteinase 3 is a major autoimmune target in systemic vasculitis. Proteinase 3 is an abundant serine protease of neutrophil granules and a major target of PR3 antineutrophil cytoplasmic autoantibodies in granulomatosis with polyangiitis. Some of the enzyme synthesized by promyelocytes in the bone marrow escape the targeting to granules and occur on the plasma membrane of naive and primed neutrophils. This membrane-associated PR3 antigen may represent pro-PR3, mature PR3, or both forms Homo sapiens