BRENDA - Enzyme Database
show all sequences of 3.4.21.76

A monoclonal antibody (MCPR3-7) interfering with the activity of proteinase 3 by an allosteric mechanism

Hinkofer, L.C.; Seidel, S.A.; Korkmaz, B.; Silva, F.; Hummel, A.M.; Braun, D.; Jenne, D.E.; Specks, U.; J. Biol. Chem. 288, 26635-26648 (2013)

Data extracted from this reference:

Application
Application
Commentary
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 (Commentary)
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
Engineering
Protein Variants
Commentary
Organism
S195A
site-directed mutagenesis, cDNA construction of a catalytically inactive active site enyzme mutant lacking the codons for the N-terminal activation dipeptide, DELTAPR3ctp-S195A
Homo sapiens
Inhibitors
Inhibitors
Commentary
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
Commentary
Textmining
Homo sapiens
P24158
-
-
Posttranslational Modification
Posttranslational Modification
Commentary
Organism
proteolytic modification
the pro-enzyme zymogen has to be proteolytically activated
Homo sapiens
Source Tissue
Source Tissue
Commentary
Organism
Textmining
neutrophil
enzyme expression on neutrophil membranes
Homo sapiens
-
promyelocyte
-
Homo sapiens
-
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
Substrate Product ID
5-TAMRA-VADnVADYQ-DAP(CF) + H2O
a fluorescence resonance energy transfer, FRET, substrate. The reaction is inhibited by antibody MCPR3-7 binding
732115
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
732115
Homo sapiens
?
-
-
-
?
Ahx-PYFA-4-nitroanilide + H2O
the reaction is inhibited by antibody MCPR3-7 binding
732115
Homo sapiens
?
-
-
-
?
Boc-Ala-ONp + H2O
the reaction is not inhibited by antibody MCPR3-7 binding
732115
Homo sapiens
?
-
-
-
?
Boc-Ala-Pro-nVal-SBzl + H2O
the reaction is not inhibited by antibody MCPR3-7 binding
732115
Homo sapiens
?
-
-
-
?
For-Ala-Ala-Pro-Abu-SBzl + H2O
the reaction is partly inhibited by antibody MCPR3-7 binding
732115
Homo sapiens
?
-
-
-
?
Synonyms
Synonyms
Commentary
Organism
PR3
-
Homo sapiens
proteinase 3
-
Homo sapiens
Temperature Optimum [°C]
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
37
-
assay at
Homo sapiens
pH Optimum
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
7.4
-
assay at
Homo sapiens
Application (protein specific)
Application
Commentary
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) (protein specific)
Commentary
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
Engineering (protein specific)
Protein Variants
Commentary
Organism
S195A
site-directed mutagenesis, cDNA construction of a catalytically inactive active site enyzme mutant lacking the codons for the N-terminal activation dipeptide, DELTAPR3ctp-S195A
Homo sapiens
Inhibitors (protein specific)
Inhibitors
Commentary
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
Posttranslational Modification (protein specific)
Posttranslational Modification
Commentary
Organism
proteolytic modification
the pro-enzyme zymogen has to be proteolytically activated
Homo sapiens
Source Tissue (protein specific)
Source Tissue
Commentary
Organism
Textmining
neutrophil
enzyme expression on neutrophil membranes
Homo sapiens
-
promyelocyte
-
Homo sapiens
-
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
ID
5-TAMRA-VADnVADYQ-DAP(CF) + H2O
a fluorescence resonance energy transfer, FRET, substrate. The reaction is inhibited by antibody MCPR3-7 binding
732115
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
732115
Homo sapiens
?
-
-
-
?
Ahx-PYFA-4-nitroanilide + H2O
the reaction is inhibited by antibody MCPR3-7 binding
732115
Homo sapiens
?
-
-
-
?
Boc-Ala-ONp + H2O
the reaction is not inhibited by antibody MCPR3-7 binding
732115
Homo sapiens
?
-
-
-
?
Boc-Ala-Pro-nVal-SBzl + H2O
the reaction is not inhibited by antibody MCPR3-7 binding
732115
Homo sapiens
?
-
-
-
?
For-Ala-Ala-Pro-Abu-SBzl + H2O
the reaction is partly inhibited by antibody MCPR3-7 binding
732115
Homo sapiens
?
-
-
-
?
Temperature Optimum [°C] (protein specific)
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
37
-
assay at
Homo sapiens
pH Optimum (protein specific)
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
7.4
-
assay at
Homo sapiens
General Information
General Information
Commentary
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
General Information (protein specific)
General Information
Commentary
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
Other publictions for EC 3.4.21.76
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Synonyms
Temperature Optimum [°C]
Temperature Range [°C]
Temperature Stability [°C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [°C] (protein specific)
Temperature Range [°C] (protein specific)
Temperature Stability [°C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
752863
Grzywa
Proteinase 3 phosphonic inhib ...
Homo sapiens
Biochimie
166
142-149
2019
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-
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16
12
4
-
-
1
-
1
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-
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18
-
2
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16
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12
4
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1
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18
-
-
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-
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-
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3
3
-
16
16
754755
Mirea
Increased proteinase 3 and ne ...
Homo sapiens
Mol. Med.
25
16
2019
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1
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2
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2
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1
3
3
1
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752871
Popow-Stellmaszyk
Design, synthesis, and enzyma ...
Homo sapiens
Bioconjug. Chem.
29
1576-1583
2018
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1
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753664
Fu
Extended cleavage specificity ...
Homo sapiens, Xenopus laevis
Front. Immunol.
9
2387
2018
-
-
1
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2
-
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5
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1
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1
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28
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6
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28
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2
2
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753821
Chen
JMJD3 is involved in neutroph ...
Homo sapiens
Int. Immunopharmacol.
59
40-46
2018
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1
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1
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3
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1
2
2
1
-
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754329
Yang
Membrane-associated proteinas ...
Homo sapiens
J. Immunol.
201
1389-1399
2018
-
-
-
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2
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1
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6
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6
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2
2
-
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754395
Guarino
Exploiting the S4-S5 specific ...
Homo sapiens
J. Med. Chem.
61
1858-1870
2018
-
-
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-
-
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11
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2
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1
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1
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4
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11
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1
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-
1
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-
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-
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1
1
-
-
-
754130
Martin
Proteinase 3 is a phosphatidy ...
Homo sapiens
J. Biol. Chem.
291
10476-10489
2016
-
-
1
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2
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3
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2
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1
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1
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1
3
3
1
-
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731482
Hwang
Synthesis and pharmacological ...
Homo sapiens
Bioorg. Med. Chem.
23
1123-1134
2015
-
1
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-
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-
25
-
1
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2
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1
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1
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24
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25
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1
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1
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1
1
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731997
Hinkofer
Allosteric modulation of prote ...
Homo sapiens
J. Autoimmun.
59
43-52
2015
-
1
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2
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3
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1
1
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752941
Hwang
Synthesis and pharmacological ...
Homo sapiens
Bioorg. Med. Chem.
23
1123-1134
2015
-
1
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-
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-
25
-
2
1
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2
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1
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1
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1
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732316
Budnjo
Reversible ketomethylene-based ...
Homo sapiens
J. Med. Chem.
57
9396-9408
2014
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2
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2
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732115
Hinkofer
A monoclonal antibody (MCPR3-7 ...
Homo sapiens
J. Biol. Chem.
288
26635-26648
2013
-
1
1
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1
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2
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1
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2
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717959
Kantari
Molecular analysis of the memb ...
Homo sapiens
J. Leukoc. Biol.
90
941-950
2011
-
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1
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8
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2
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2
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1
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718119
Kim
Membrane-bound proteinase 3 an ...
Homo sapiens
Mol. Immunol.
48
1966-1974
2011
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1
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718391
Relle
Comparative aspects of murine ...
Mus musculus
Rheumatol. Int.
31
1105-1111
2011
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707117
Wysocka
The new fluorogenic substrates ...
Homo sapiens
Anal. Biochem.
399
196-201
2010
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19
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19
19
707129
Wysocka
Highly specific substrates of ...
Homo sapiens
Anal. Chem.
82
3883-3889
2010
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1
707736
Dou
Utilization of the 1,2,3,5-thi ...
Homo sapiens
Bioorg. Med. Chem.
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Hajjar
Structures of human proteinase ...
Homo sapiens, Mus musculus
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1
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3
1
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709372
Kuhl
Mapping of conformational epit ...
Homo sapiens, Hylobates pileatus, Macaca mulatta, Pan troglodytes verus
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717507
Abdgawad
Elevated neutrophil membrane e ...
Homo sapiens
Clin. Exp. Immunol.
161
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2010
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1
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717575
Kaellquist
Neutrophil elastase and protei ...
Homo sapiens
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316
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2010
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1
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718191
Broemstrup
How does proteinase 3 interact ...
Homo sapiens
Phys. Chem. Chem. Phys.
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695610
Damoiseaux
A novel enzyme-linked immunoso ...
Homo sapiens
Ann. Rheum. Dis.
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1
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2
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1
1
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-
1
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1
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1
-
-
-
-
-
-
-
-
-
-
-
-
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697411
Armstrong
Tumour necrosis factor-alpha p ...
Homo sapiens
Clin. Exp. Immunol.
156
336-343
2009
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-
-
-
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-
-
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2
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1
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1
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2
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1
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
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707316
Hu
Coexpression of CD177 and memb ...
Homo sapiens
Arthritis Rheum.
60
1548-1557
2009
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-
-
-
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1
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1
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2
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1
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1
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-
-
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1
1
1
1
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707322
Joosten
Inflammatory arthritis in casp ...
Homo sapiens, Mus musculus
Arthritis Rheum.
60
3651-3662
2009
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1
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1
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1
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4
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1
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1
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1
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-
1
-
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3
3
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707338
Hu
Membrane-bound proteinase 3 an ...
Homo sapiens
Autoimmun. Rev.
8
510-514
2009
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1
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1
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1
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1
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2
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1
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1
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3
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-
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1
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1
-
-
-
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1
1
1
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709030
Korkmaz
Catalytic activity and inhibit ...
Homo sapiens
J. Biol. Chem.
284
19896-19902
2009
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1
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2
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3
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1
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1
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2
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1
-
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709349
Kahn
Neutrophil-derived proteinase ...
Homo sapiens
J. Immunol.
182
7906-7915
2009
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1
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2
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-
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2
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1
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1
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1
-
-
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709431
Geyer
Wegeners Granulomatosis presen ...
Homo sapiens
J. Med. Case Rep.
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19
2009
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1
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1
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1
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709688
Hajjar
Challenges in pKa predictions ...
Homo sapiens
J. Phys. Chem. A
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11783-11792
2009
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1
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1
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709758
Hua
T-lymphocytes and disease mech ...
Homo sapiens
Kidney Blood Press. Res.
32
389-398
2009
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1
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4
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3
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1
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-
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1
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4
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-
-
-
-
-
-
-
-
-
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1
1
-
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710661
Piesche
Characterization of HLA-DR-res ...
Homo sapiens
Vaccine
27
4718-4723
2009
1
1
1
-
-
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1
-
-
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-
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2
-
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1
-
-
5
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-
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2
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-
-
-
-
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-
-
-
1
1
1
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-
-
-
-
1
-
-
-
-
-
-
-
-
-
1
-
5
-
-
-
-
-
-
-
-
-
-
-
-
-
1
1
-
-
-
683193
Korkmaz
Neutrophil elastase, proteinas ...
Homo sapiens
Biochimie
90
227-242
2008
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1
1
1
-
-
6
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4
-
-
-
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3
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6
-
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11
1
2
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1
1
-
-
-
1
-
-
1
1
-
1
-
-
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6
-
-
4
-
-
-
-
-
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6
-
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11
1
-
-
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-
1
1
-
1
-
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-
686192
Csernok
Pathways to ANCA production: F ...
Homo sapiens, Mus musculus
Clin. Rev. Allergy Immunol.
34
300-306
2008
1
2
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-
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3
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1
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2
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4
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-
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1
2
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-
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-
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1
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2
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-
-
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-
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698376
Kasuga
Pulmonary complications resemb ...
Homo sapiens
Intern. Med.
47
1211-1214
2008
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1
-
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-
-
-
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2
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-
-
-
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-
-
2
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-
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-
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-
-
1
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-
-
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-
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-
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-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
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-
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684453
Mueller
Human proteinase 3 (PR3) and i ...
Homo sapiens
Ann. N. Y. Acad. Sci.
1109
84-92
2007
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1
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1
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4
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2
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-
3
-
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2
-
2
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-
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-
1
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1
-
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4
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-
-
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3
-
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2
-
-
-
-
-
-
-
-
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-
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-
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685785
Kantari
Proteinase 3, the Wegener auto ...
Homo sapiens
Blood
110
4086-4095
2007
1
1
1
-
1
-
1
-
3
-
-
-
-
3
-
-
-
-
-
1
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-
-
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3
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-
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1
1
1
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-
1
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1
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3
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1
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-
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-
-
-
-
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-
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-
-
-
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686753
Hajjar
Differences in the substrate b ...
Homo sapiens, Mus musculus, Rattus norvegicus
FEBS Lett.
581
5685-5690
2007
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9
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687439
Specks
Functional significance of Asn ...
Homo sapiens
J. Biochem.
141
101-112
2007
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1
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1
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1
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1
1
1
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3
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1
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4
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1
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1
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1
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1
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687566
Korkmaz
Influence of charge distributi ...
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282
1989-1997
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22
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2
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1
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-
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5
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1
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22
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687618
Vong
Annexin 1 cleavage in activate ...
Homo sapiens
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1
1
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1
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1
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1
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1
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1
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688215
Bauer
Proteinase 3 and CD177 are exp ...
Homo sapiens
J. Leukoc. Biol.
81
458-464
2007
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1
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1
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4
1
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4
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1
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688708
Villegas-Mendez
Proteolysis of the endothelial ...
Homo sapiens
J. Thromb. Haemost.
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2007
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1
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1
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1
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1
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689931
Borelli
The crystal structure of the s ...
Candida albicans
Proteins
68
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2007
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1
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1
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1
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1
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1
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664451
Csernok
Wegener autoantigen induces ma ...
Homo sapiens
Blood
107
4440-4448
2006
-
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1
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2
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1
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2
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2
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-
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1
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1
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2
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666199
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29721
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1
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29722
Dolman
Determination of proteinase 3- ...
Homo sapiens
FEBS Lett.
314
117-121
1992
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2
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2
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29718
Labbaye
Wegener autoantigen and myelob ...
Homo sapiens
Proc. Natl. Acad. Sci. USA
88
9253-9256
1991
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1
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2
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2
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29719
Rao
Characterization of proteinase ...
Homo sapiens
J. Biol. Chem.
266
9540-9548
1991
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4
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