Information on EC 3.4.21.76 - Myeloblastin

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
3.4.21.76
-
RECOMMENDED NAME
GeneOntology No.
Myeloblastin
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
Hydrolysis of proteins, including elastin, by preferential cleavage: -Ala-/- > -Val-/-
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
128028-50-2
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
-
neutrophil serine proteases, proteinase 3 and human neutrophil elastase, share high sequence similarity, but have different substrate specificities and functions
malfunction
metabolism
physiological function
additional information
-
proteinase 3 is an abundant serine protease with high similarity to neutrophil elastase
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(7-methoxycoumarin-4-yl)acetyl-Ala-Ala-Ala-Ala-Lys-Gly-Asp-Dpa-NH2 + H2O
?
show the reaction diagram
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Ala-Ala-Pro-Leu-Lys-Gly-Asp-Dpa-NH2 + H2O
?
show the reaction diagram
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Ala-Ala-Pro-Val-Lys-Gly-Asp-Dpa-NH2 + H2O
?
show the reaction diagram
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Lys(2-picolinoyl)-Tyr-Asp-Ala-Lys-Gly-Asp-Dpa-NH2 + H2O
?
show the reaction diagram
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Lys(2-picolinoyl)-Tyr-Asp-Ile-Lys-Gly-Asp-Dpa-NH2 + H2O
?
show the reaction diagram
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Lys(2-picolinoyl)-Val-Glu-Ala-Lys-Gly-Asp-Dpa-NH2 + H2O
?
show the reaction diagram
-
-
-
?
(VGVAPG)2V + H2O
?
show the reaction diagram
-
pH 8.6, room temperature
-
-
?
(VGVAPG)3V + H2O
?
show the reaction diagram
-
pH 8.6, room temperature
-
-
?
2-aminobenzoyl-APEEIM(o)DRQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-APEEIMDRQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-APEEIMMDRQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-EAIPMSIPPEVKFNKQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-EAIPMSIPQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-GIATFCM(o)LM(o)PEQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-GIATFCMLMPEQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-IVSARMAPEEIIMDRQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-MMRCAQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-TFCM(o)LEQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-TFCMLEQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide) + H2O
?
show the reaction diagram
-
-
-
-
?
2-aminobenzoyl-VADCAQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-VAECCQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-VSARQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
show the reaction diagram
-
-
-
?
5-TAMRA-VADnVADYQ-DAP(CF) + H2O
?
show the reaction diagram
-
a fluorescence resonance energy transfer, FRET, substrate. The reaction is inhibited by antibody MCPR3-7 binding
-
-
?
5-TAMRA-VADnVRDYQ-diaminopropionyl-fluorescein + H2O
?
show the reaction diagram
-
fluorogenic substrate
-
-
?
Abz-APEEIMDDQ-ethylene diamine 2,4 dinitrophenyl + H2O
?
show the reaction diagram
37C, pH 7.4, 150 mM NaCl, kcat/KM = 2.5/mM/s
-
-
?
Abz-APEEIMDQQ-ethylene diamine 2,4 dinitrophenyl + H2O
?
show the reaction diagram
37C, pH 7.4, 150 mM NaCl, kcat/KM = 2/mM/s
-
-
?
Abz-APEEIMDRQ-ethylene diamine 2,4 dinitrophenyl + H2O
?
show the reaction diagram
37C, pH 7.4, 150 mM NaCl, kcat/KM = 14.6/mM/s
-
-
?
Abz-APEEIMDRY-ethylene diamine 2,4 dinitrophenyl + H2O
?
show the reaction diagram
37C, pH 7.4, 150 mM NaCl, kcat/KM = lower than 1/mM/s
-
-
?
Abz-APEEIMDRYQ-ethylene diamine 2,4 dinitrophenyl + H2O
?
show the reaction diagram
37C, pH 7.4, 150 mM NaCl, kcat/KM = 3.2/mM/s
-
-
?
Abz-APEEIMDYQ-ethylene diamine 2,4 dinitrophenyl + H2O
?
show the reaction diagram
37C, pH 7.4, 150 mM NaCl, kcat/KM = 2.6/mM/s
-
-
?
Abz-APEEIMPRQ-ethylene diamine 2,4 dinitrophenyl + H2O
?
show the reaction diagram
37C, pH 7.4, 150 mM NaCl, kcat/KM = lower than 1/mM/s
-
-
?
Abz-APEEIMRRQ-ethylene diamine 2,4 dinitrophenyl + H2O
?
show the reaction diagram
37C, pH 7.4, 150 mM NaCl, kcat/KM = lower than 1/mM/s
-
-
?
Abz-GIATDCRDRPEQ-EDDnp + H2O
?
show the reaction diagram
-
-
-
-
?
Abz-GIATFCDLMPEQ-EDDnp + H2O
?
show the reaction diagram
-
-
-
-
?
Abz-GIATFCMKMPEQ-EDDnp + H2O
?
show the reaction diagram
-
-
-
-
?
Abz-GIATFCMLMPEQ-EDDnp + H2O
?
show the reaction diagram
-
-
-
-
?
Abz-GIATFCRLMPEQ-EDDnp + H2O
?
show the reaction diagram
-
-
-
-
?
Abz-GRATFCMLMPEQ-EDDnp + H2O
?
show the reaction diagram
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide) + H2O
Abz-Tyr-Tyr-Abu + 5-amino-2-nitrobenzamide
show the reaction diagram
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ala-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Ala-NH2
show the reaction diagram
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Arg-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Arg-NH2
show the reaction diagram
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Asn-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Asn-NH2
show the reaction diagram
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Asp-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Asp-NH2
show the reaction diagram
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Gln-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Gln-NH2
show the reaction diagram
-
is hydrolyzed by PR3 within 20 min, yielding (5-amino-2-nitrobenzoyl)-Gln-NH2 and Abz-Tyr-Tyr-Abu fragments with retention times of 10.4 and 12.3 min, respectively
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Glu-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Glu-NH2
show the reaction diagram
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Gly-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Gly-NH2
show the reaction diagram
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-His-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-His-NH2
show the reaction diagram
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ile-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Ile-NH2
show the reaction diagram
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Leu-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Leu-NH2
show the reaction diagram
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Lys-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Lys-NH2
show the reaction diagram
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Phe-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Phe-NH2
show the reaction diagram
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Pro-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Pro-NH2
show the reaction diagram
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ser-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Ser-NH2
show the reaction diagram
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Thr-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Thr-NH2
show the reaction diagram
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Trp-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Trp-NH2
show the reaction diagram
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Tyr-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Tyr-NH2
show the reaction diagram
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Val-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Val-NH2
show the reaction diagram
-
-
-
-
?
Abz-Tyr-Tyr-Abu-ANB-NH2 + H2O
?
show the reaction diagram
-
a fluorescence resonance energy transfer, FRET, substrate. The reaction is inhibited by antibody MCPR3-7 binding
-
-
?
Abz-VADCADQ-(2,4-dinitrophenyl)ethylenediamine + H2O
?
show the reaction diagram
-
-
-
-
?
Abz-VADCADQ-EDDnp + H2O
?
show the reaction diagram
-
-
-
-
?
Abz-VADCADQ-ethylene diamine 2,4 dinitrophenyl + H2O
?
show the reaction diagram
Abz-VADCADQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
show the reaction diagram
-
-
-
-
?
Abz-VADCADRQ-EDDnp + H2O
Abz-VADCA + DRQ-EDDnp
show the reaction diagram
-
-
-
-
?
Abz-VADCADRY(NO2) + H2O
?
show the reaction diagram
37C, pH 7.4, 150 mM NaCl, kcat/KM = 651/mM/s
-
-
?
Abz-VADCADY(NO2) + H2O
?
show the reaction diagram
37C, pH 7.4, 150 mM NaCl, kcat/KM = 630/mM/s
-
-
?
Abz-VADCAPY(NO2) + H2O
?
show the reaction diagram
37C, pH 7.4, 150 mM NaCl, kcat/KM = lower than 1/mM/s
-
-
?
Abz-VADCAQ-EDDnp + H2O
?
show the reaction diagram
-
-
-
-
?
Abz-VADCAQ-ethylene diamine 2,4 dinitrophenyl + H2O
?
show the reaction diagram
37C, pH 7.4, 150 mM NaCl, kcat/KM = 292/mM/s
-
-
?
Abz-VADCARY(NO2) + H2O
?
show the reaction diagram
37C, pH 7.4, 150 mM NaCl, kcat/KM = 3.8/mM/s
-
-
?
Abz-VADCAY(NO2) + H2O
?
show the reaction diagram
37C, pH 7.4, 150 mM NaCl, kcat/KM = 10.9/mM/s
-
-
?
Abz-VADCDDRQ-EDDnp + H2O
Abz-VADCD + DRQ-EDDnp
show the reaction diagram
-
-
-
-
?
Abz-VADCRDRQ-EDDnp + H2O
Abz-VADCR + DRQ-EDDnp
show the reaction diagram
Abz-VADnVADRQ-EDDnp + H2O
Abz-VADnVA + DRQ-EDDnp
show the reaction diagram
-
-
-
-
?
Abz-VADnVADYQ-EDDnp + H2O
?
show the reaction diagram
-
-
-
-
?
Abz-VADnVRDRQ-EDDnp + H2O
Abz-VADnVR + DRQ-EDDnp
show the reaction diagram
-
-
-
-
?
Abz-VADnVRDYQ-EDDnp + H2O
?
show the reaction diagram
-
-
-
-
?
Abz-VADVKDRQ-EDDnp + H2O
Abz-VADVK + DRQ-EDDnp
show the reaction diagram
-
-
-
-
?
Abz-VADVKDRQ-ethylene diamine 2,4 dinitrophenyl + H2O
?
show the reaction diagram
-
-
-
-
?
Abz-Val-Ala-Asp-Nvl-Ala-Asp-Arg-Gln-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
show the reaction diagram
-
-
-
-
?
Abz-VARCRDRQ-EDDnp + H2O
Abz-VARCR + DRQ-EDDnp
show the reaction diagram
-
-
-
-
?
Ac-Ala-Ala-Pro-Ala-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
?
Ac-Ala-Ala-Pro-Val-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
?
Ahx-PYFA-4-nitroanilide + H2O
?
show the reaction diagram
-
the reaction is inhibited by antibody MCPR3-7 binding
-
-
?
annexin 1 + H2O
?
show the reaction diagram
-
proteinase 3 is the main enzyme responsible for cleavage in the N terminus region of the protein
-
-
?
APG(VGVAPG)2V + H2O
?
show the reaction diagram
-
pH 8.6, room temperature
-
-
?
azocasein + H2O
fragments of azocasein
show the reaction diagram
-
-
-
-
-
BID + H2O
?
show the reaction diagram
-
37C, Bid = BH3 interacting domain death agonist
-
-
?
Boc-Ala-Ala-Nva-SBzl + H2O
?
show the reaction diagram
-
-
-
?
Boc-Ala-Ala-Nva-thiobenzyl ester + H2O
?
show the reaction diagram
-
-
-
-
?
Boc-Ala-Ala-Nva-thiobenzylester + H2O
?
show the reaction diagram
-
pH 8.6, room temperature
-
-
?
Boc-Ala-Ala-Pro-Ala-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
?
Boc-Ala-ONp + H2O
?
show the reaction diagram
-
the reaction is not inhibited by antibody MCPR3-7 binding
-
-
?
Boc-Ala-Pro-Nva-4-chloro-thiobenzyl ester + H2O
?
show the reaction diagram
Boc-Ala-Pro-Nva-SBzl + H2O
?
show the reaction diagram
-
-
-
?
Boc-Ala-Pro-Nva-thiobenzylester + H2O
?
show the reaction diagram
Boc-Ala-Pro-nVal-SBzl + H2O
?
show the reaction diagram
-
the reaction is not inhibited by antibody MCPR3-7 binding
-
-
?
casein + H2O
?
show the reaction diagram
-
-
-
-
?
Collagen type IV + H2O
Hydrolyzed collagen type IV
show the reaction diagram
-
no or minimal activity against interstitial collagens type I and III
-
-
-
DRDAVDRDID + H2O
?
show the reaction diagram
-
-
-
-
?
DVARVKDRQEG + H2O
?
show the reaction diagram
-
-
-
-
?
Elastin + H2O
Hydrolyzed elastin
show the reaction diagram
endothelial cell protein C receptor + H2O
?
show the reaction diagram
-
PR3 produces multiple cleavages, with early products including 20 kDa N-terminal and C-terminal (after Lys176) fragments. High affinity interaction between PR3 and the endothelial cell protein C receptor (KD of 18.5102 nanomol)
-
-
?
Fibronectin + H2O
Hydrolyzed fibronectin
show the reaction diagram
-
-
-
-
-
For-Ala-Ala-Pro-Abu-SBzl + H2O
?
show the reaction diagram
-
the reaction is partly inhibited by antibody MCPR3-7 binding
-
-
?
FRET + H2O
?
show the reaction diagram
-
-
-
-
?
GDVAVYEEN + H2O
?
show the reaction diagram
-
-
-
-
?
Hemoglobin + H2O
Hydrolyzed hemoglobin
show the reaction diagram
-
-
-
-
-
IL-18 + H2O
?
show the reaction diagram
-
-
-
-
?
IL-1beta + H2O
?
show the reaction diagram
-
-
-
-
?
IL-32 + H2O
?
show the reaction diagram
kininogen + H2O
?
show the reaction diagram
-
PR3 incubated with kininogen, or a synthetic peptide derived from kininogen, induces breakdown and release of a novel tridecapeptide termed PR3-kinin, NH2-MKRPPGFSPFRSS-COOH, consisting of bradykinin with two additional amino acids on each terminus. The reaction is specific. PR3-kinin binds to and activates human kinin B1 receptors, but does not bind to B2 receptors, expressed by transfected HEK293 cells in vitro. PR3-kinin is processed to bradykinin and des-Arg-bradykinin by plasma kallikrein. PR3 proteolyzes kininogen in a dose-dependent and specific manner. PR3 in neutrophil extracts induces kininogen proteolysis and induces release of bradykinin-like peptides from kininogen
-
-
?
laminin + H2O
fragments of laminin
show the reaction diagram
-
-
-
-
-
Mca-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide) + H2O
?
show the reaction diagram
-
-
-
-
?
MeO-Suc-Ala-Ala-Pro-Val-4-nitroanilide + H2O
MeO-Suc-Ala-Ala-Pro-Val + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
MeO-Suc-Lys-(pico)-Ala-Pro-Val-thiobenzylester + H2O
?
show the reaction diagram
-
25C
-
-
?
MeOSuc-AAPV-4-nitroanilide + H2O
MeOSuc-AAPV + 4-nitroaniline
show the reaction diagram
MeOSuc-AIPM-4-nitroanilide + H2O
MeOSuc-AIPM + 4-nitroaniline
show the reaction diagram
MeOSuc-Ala-Ala-Pro-Val-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
?
MeOSuc-Lys(2-picolinoyl)-Ala-Pro-Val-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
?
MeOSuc-Lys(2-picolinoyl)-Tyr-Asp-Ala-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
?
MeOSuc-Lys(2-picolinoyl)-Tyr-Asp-Val-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
?
methoxysuccinyl-lysyl-(2-picolinoyl)-Ala-Pro-Val-p-nitroanilide + H2O
?
show the reaction diagram
-
pH 7.4, 150 mM NaCl
-
-
?
methoxysuccinyl-lysyl-(2-picolinoyl)-Ala-Pro-Val-thiobenzylester + H2O
?
show the reaction diagram
-
pH 7.4, 150 mM NaCl, 3 mM 4,4-dithiodipyridine
-
-
?
N-Boc-3-[2-(2'-imidazolyl)benzoxazol-5-yl]-Ala-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide) + H2O
?
show the reaction diagram
-
-
-
-
?
N-Boc-3-[2-(2'-methoxy-4'-dimethylaminophenyl)benzoxazol-5-yl]-Ala-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide) + H2O
?
show the reaction diagram
-
-
-
-
?
N-Boc-3-[2-(2-quinolinyl)benzoxazol-5-yl]-Ala-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide) + H2O
?
show the reaction diagram
-
-
-
-
?
N-Boc-3-[2-[2-(1'-methyl)pyrrolo]benzoxazol-5-yl]-Ala-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide) + H2O
?
show the reaction diagram
-
is the most efficient PR3 substrate
-
-
?
N-Boc-Ala-o-nitrophenol + H2O
?
show the reaction diagram
-
37C, pH 7.4
-
-
?
N-methoxysuccinyl-Ala-Ala-Pro-Val-pNA + H2O
?
show the reaction diagram
-
-
-
-
?
N-t-Boc-L-alanine-p-nitrophenyl-ester + H2O
?
show the reaction diagram
-
-
-
?
NF-kappaB + H2O
?
show the reaction diagram
-
-
-
-
?
NFkappaB + H2O
?
show the reaction diagram
-
-
-
-
?
nuclear factor-kappaB + H2O
?
show the reaction diagram
-
-
-
-
?
oxidized insulin B chain + H2O
?
show the reaction diagram
p21 + H2O
?
show the reaction diagram
p21 protein + H2O
?
show the reaction diagram
PAR-2 + H2O
?
show the reaction diagram
-
PAR-2 = protease-activated receptor 2
-
-
?
Peptidyl thiobenzyl ester + H2O
?
show the reaction diagram
-
the preferred P1 residue is a small hydrophobic amino acid such as aminobutyric acid, norvaline, valine or alanine, in decreasing order of preference
-
-
-
pro-TNFalpha + H2O
?
show the reaction diagram
-
-
-
-
?
procaspase 3 + H2O
?
show the reaction diagram
-
PR3 can cleave membrane-associated procaspase 3 into a 22 kDa fragment
-
-
?
procaspase-3 + H2O
?
show the reaction diagram
proIL-1beta + H2O
active IL-1beta + ?
show the reaction diagram
-
is processed by PR3 or caspase 1
-
-
?
protease-activated receptor-2
?
show the reaction diagram
-
PR3 may possess the capacity to interact and activate protease-activated receptor-2 expressing antigen-presenting cells and thereby potentially link this proinflammatory activity to the initiation of an adaptive immune response (induction of PR3-specific T cells)
-
-
?
protease-activated receptor-2 + H2O
?
show the reaction diagram
-
-
-
-
?
RDVARCRDRQEG + H2O
?
show the reaction diagram
-
-
-
-
?
RDVARCRDRQQG + H2O
?
show the reaction diagram
-
-
-
-
?
Suc-AAA-4-nitroanilide + H2O
Suc-AAA + 4-nitroaniline
show the reaction diagram
Suc-AAPL-4-nitroanilide + H2O
Suc-AAPL + 4-nitroaniline
show the reaction diagram
Suc-AAPV-4-nitroanilide + H2O
Suc-AAPV + 4-nitroaniline
show the reaction diagram
Suc-Ala-Ala-Asp-Val-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
?
Suc-Ala-Ala-Glu-Val-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
?
Suc-Ala-Ala-Pro-2-aminobutyric acid-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
?
Suc-Ala-Ala-Pro-Ala-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
?
Suc-Ala-Ala-Pro-Ile-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
?
Suc-Ala-Ala-Pro-Nva-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
?
Suc-Ala-Ala-Pro-Val-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
?
Suc-Ala-Tyr-Leu-Val-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
?
Suc-Ala4-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
?
Suc-Leu-Val-Glu-Ala-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
?
Succinyl-Ala-Ala-norvaline thiobenzyl ester + H2O
?
show the reaction diagram
-
-
-
-
-
surfactant protein D + H2O
?
show the reaction diagram
Tert-Butyloxycarbonyl-Ala-Ala-Ala thiobenzyl ester + H2O
?
show the reaction diagram
-
-
-
-
-
Tert-Butyloxycarbonyl-Ala-Ala-Ile thiobenzyl ester + H2O
?
show the reaction diagram
-
-
-
-
-
Tert-Butyloxycarbonyl-Ala-Ala-Met thiobenzyl ester + H2O
?
show the reaction diagram
-
-
-
-
-
Tert-Butyloxycarbonyl-Ala-Ala-norvaline thiobenzyl ester + H2O
?
show the reaction diagram
-
best substrate
-
-
-
Tert-Butyloxycarbonyl-Ala-Ala-Val thiobenzyl ester + H2O
?
show the reaction diagram
-
-
-
-
-
TNF-alpha + H2O
?
show the reaction diagram
-
-
-
-
?
tumour necrosis factor-alpha + H2O
?
show the reaction diagram
-
PR-3-mediated cleavage of tumour necrosis factor-alpha in usual interstitial pneumonia, which may have implications for future therapeutic targeting of tumour necrosis factor-alpha converting enzyme (TACE)
-
-
?
VADVKDR + H2O
?
show the reaction diagram
Val-Ala-Asp-Val-Lys-Asp-Arg + H2O
?
show the reaction diagram
-
simulations with a neutral Asp213 bound to the peptide reproduce the expected conformation of the catalytic triad: there are strong hydrogen bonds between histidine 57 and serine 195 and between histidine 57 and the aspartic acid 102. When Asp213 is ionized and in the presence of a peptide bound in the enzyme, its side chain moves away from Gly197 and toward Ser195. The resulting interaction between Asp213 and Ser195 is strong with the formation of a hydrogen bond that persists for over 90% of the simulation time. Interaction competes with the crucial Ser-His hydrogen of the catalytic triad altering the proteolytic function of the enzyme. The pKa for Asp213 is of 8.4 (with a fast empirical method or based on molecular dynamics simulations). In simulations with negatively charged form of Asp213 the interaction between the carbonyl of the P1 residue (oxyanion hole) of the substrate and Ser195 (NH) of PR3 has vanished and the favorable interactions between the enzyme and the substrate are disrupted. A strong hydrogen bond is formed between the imidazole ring of His57 and the P1 and P1' residues of the substrate (NH groups) lasting 83 and 55% of the simulation time, respectively. These hydrogen bonds compete with, or replace, the crucial ones between amino acids of the catalytic triad and in particular the Ser-His interaction
-
-
-
VARVRDR + H2O
?
show the reaction diagram
Vitronectin + H2O
Hydrolyzed vitronectin
show the reaction diagram
-
-
-
-
-
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
additional information
?
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(DL)-5-benzyl-3-(phenylsulfonylmethyl)-1-benzylhydantoin
-
-
(DL)-5-benzyl-3-(phenylsulfonylmethyl)hydantoin
-
-
(DL)-5-benzyl-3-(phenylthiomethyl)-1-benzylhydantoin
-
-
(DL)-5-benzyl-3-(phenylthiomethyl)hydantoin
-
-
(DL)-5-benzylhydantoin
-
-
(DL)-5-isobutyl-3-(phenylsulfonylmethyl)-1-benzylhydantoin
-
-
(DL)-5-isobutyl-3-(phenylsulfonylmethyl)hydantoin
-
-
(DL)-5-isobutyl-3-(phenylthiomethyl)-1-benzylhydantoin
-
-
(DL)-5-isobutyl-3-(phenylthiomethyl)hydantoin
-
-
(DL)-5-isobutylhydantoin
-
-
(E)-4-(N-(2-(1-(hydroxyimino)butyl)phenyl)sulfamoyl)phenyl pivalate
-
-
(E)-4-(N-(2-(1-(hydroxyimino)ethyl)phenyl)sulfamoyl)phenyl pivalate
-
the compound has several beneficial effects in inflammatory disease and lipopolysacchride-induced edema, overview
(E)-4-(N-(2-(1-(hydroxyimino)methyl)phenyl)sulfamoyl)phenyl pivalate
-
-
(E)-4-(N-(2-(1-(hydroxyimino)propyl)phenyl)sulfamoyl)phenyl pivalate
-
-
(E)-4-(N-(2-(1-(methoxyimino)ethyl)phenyl)sulfamoyl)phenyl pivalate
-
-
(S)-4-isobutyl-2-[(p-chlorobenzylthio)methyl]-5-benzyl-1,2,5-thiadiazolidin-3-one 1,1-dioxide
-
-
(S)-4-isobutyl-2-[(phenylthio)methyl]-1,2,5-thiadiazolidin-3-one 1,1-dioxide
-
-
(S)-4-isobutyl-5-benzyl-2-chloromethyl-1,2,5-thiadiazolidin-3-one 1,1-dioxide
-
-
(S)-4-isobutyl-5-benzyl-2-[(phenylthio)methyl]-1,2,5-thiadiazolidin-3-one 1,1-dioxide
-
-
(S)-4-isobutyl-5-[(m-carboxyl)benzyl]-2-[(phenylsulfonyl)methyl]-1,2,5-thiadiazolidin-3-one 1,1-dioxide
-
-
(S)-4-isobutyl-5-[(m-carboxymethyl)benzyl]-2-[(phenylsulfonyl)methyl]-1,2,5-thiadiazolidin-3-one 1,1-dioxide
-
-
(S)-4-isobutyl-5-[(m-carboxymethyl)benzyl]-2-[(phenylthio)methyl]-1,2,5-thiadiazolidin-3-one 1,1-dioxide
-
-
(S)-4-isobutyl-N-[(4-chlorobenzylsulfonyl)methyl]-5-benzyl-1,2,5-thiadiazolidin-3-one 1,1-dioxide
-
-
(Z)-4-(N-(2-(1-(methoxyimino)ethyl)phenyl)sulfamoyl)phenyl pivalate
-
-
2,3-diethyl-5-([1-[(phenylsulfanyl)methyl]-1H-1,2,3-triazol-4-yl]methyl)-1,2,3,5-thiatriazolidin-4-one 1,1-dioxide
-
0.00862 mM inhibits by ca. 14%
2,3-diethyl-5-[[1-(2-oxo-2-phenylethyl)-1H-1,2,3-triazol-4-yl]methyl]-1,2,3,5-thiatriazolidin-4-one 1,1-dioxide
-
0.00862 mM inhibits by ca. 10%, fits into the Pr 3 active site well and engages in multiple interactions with the enzyme
2,3-diethyl-5-[[1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl]methyl]-1,2,3,5-thiatriazolidin-4-one 1,1-dioxide
-
0.00862 mM inhibits by ca. 8%
2-(2,3-diethyl-1,1-dioxido-4-oxo-1,2,3,5-thiatriazolidin-5-yl)-N-phenylacetamide
-
0.00862 mM inhibits by ca. 13%
2-(2,3-diethyl-1,1-dioxido-4-oxo-1,2,3,5-thiatriazolidin-5-yl)-N-[2-(2-methoxyphenyl)ethyl]-3-phenylpropanamide
-
0.00862 mM inhibits by ca. 11%
2-(2,3-diethyl-1,1-dioxido-4-oxo-1,2,3,5-thiatriazolidin-5-yl)-N-[4-(morpholin-4-yl)phenyl]-3-phenylpropanamide
-
0.00862 mM inhibits by ca. 13%
2-hydroxyethyl 2-(4-(pivaloyloxy)phenylsulfonamido)benzoate
-
-
3,4-dichloroisocoumarin
-
-
4,5-bisbenzyl-2-[[(2-benzoxazolyl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
4,5-bisbenzyl-2-[[(5-phenyl-1,3,4-oxadiazol-2-yl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
4,5-bisbenzyl-2-[[(6-amino-2-benzoxazolyl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
4-(2-aminoethyl)benzenesulfonyl fluoride
-
-
4-(N-(2-(2-hydroxyethylcarbamoyl)phenyl)sulfamoyl)phenyl pivalate
-
-
4-(N-(2-acetylphenyl)sulfamoyl)phenyl 2-methylpropane-2-sulfinate
-
-
4-(N-(2-acetylphenyl)sulfamoyl)phenyl pivalate
-
-
4-(N-(2-butyrylphenyl)sulfamoyl)phenyl pivalate
-
-
4-(N-(2-formylphenyl)sulfamoyl)phenyl 2-methylpropane-2-sulfinate
-
-
4-(N-(2-formylphenyl)sulfamoyl)phenyl pivalate
-
-
4-(N-(2-pentanoyl phenyl)sulfamoyl)phenyl pivalate
-
-
4-(N-(2-propionylphenyl)sulfamoyl)phenyl pivalate
-
-
4-benzyl-5-methyl-2-[[(2-benzoxazolyl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
4-isobutyl-5-methyl-2-[[(2-benzoxazolyl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
4-isobutyl-5-methyl-2-[[(3-phenyl-1,2,4-oxadiazol-5-yl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
4-isobutyl-5-methyl-2-[[(4,5-diphenyl-2-oxazolyl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
4-isobutyl-5-methyl-2-[[(5-phenyl-1,3,4-oxadiazol-2-yl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
4-isobutyl-5-methyl-2-[[(5-phenyl-2-benzoxazoyl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
4-isobutyl-5-methyl-2-[[2-benzothiazolthio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
5-benzyl-4-isobutyl-2-[[(2-benzoxazolyl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
5-benzyl-4-isobutyl-2-[[(3-phenyl-1,2,4-oxadiazol-5-yl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
5-benzyl-4-isobutyl-2-[[(4,5-diphenyl-2-oxazolyl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
5-benzyl-4-isobutyl-2-[[(5-phenyl-1,3,4-oxadiazol-2-yl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
5-benzyl-4-isobutyl-2-[[(5-phenyl-2-benzoxazoyl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
5-benzyl-4-isobutyl-2-[[2-benzothiazolthio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
7-Amino-4-chloro-3-(2-bromoethoxy)isocoumarin
-
-
Abz-VADnV[PSI](COCH2)ADYQ-EDDnp
-
best inhibitor, selective for proteinase 3, displays a competitive and reversible inhibition mechanism
alpha-1-Proteinase inhibitor
-
inhibits the enzyme, inhibition is implicated by anti-neutrophil cytoplasmic antibodies with proteinase 3 specificity
-
alpha-1-proteinase inhibitor serpin
-
-
-
Alpha1-antitrypsin
-
alpha1-PI
-
-
-
alpha1-protease inhibitor
-
alpha1-proteinase
-
does not inhibit when PR3 is bound to the outer cell surface of neutrophils
-
Alpha1-proteinase inhibitor
-
alpha2-Macroglobulin
-
-
-
anti-neutrophil cytoplasmic antibodies with proteinase 3 specificity
-
screening: a great majority of PR3-ANCA has inhibitory capacity towards the enzyme, overview. PR3-ANCA with inhibitory properties bind to the active site surface of proteinase 3. Epitopes of inhibitory PR3-ANCA are not masked by elafin
-
anti-PR3
-
partially inhibits PR3-induced kininogen reaction
-
benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone
Chloromethylketones
-
-
diisopropyl fluorophosphate
-
-
diisopropylfluorophosphate
-
irreversible inhibition
Eglin c
elafin
-
ethyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)benzamido)benzoate
-
-
ethyl 2-(4-(pivaloyloxy)benzamido)benzoate
-
-
lactacystin
MeO-Suc-AAPA-chloromethyl ketone
methyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)benzamido)benzoate
-
-
methyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)phenylsulfonamide)benzoate
-
-
methyl 2-(4-(pivaloyloxy)benzamido)benzoate
-
-
methyl 2-(4-pivalamidophenylsulfonamido)benzoate
-
-
MNEI
-
-
-
MNEI serpin B1
-
-
-
monocyte-neutrophil elastase inhibitor
-
-
-
N-(1,3-benzodioxol-5-yl)-2-(2,3-diethyl-1,1-dioxido-4-oxo-1,2,3,5-thiatriazolidin-5-yl)-3-phenylpropanamide
-
0.00862 mM inhibits by ca. 23%
pefabloc
-
-
phenylmethylsulfonyl fluoride
-
-
Phenylmethylsulphonylfluoride
-
-
phosphatidylinositol-specific phospholipase C
-
-
-
PI-1
-
-
-
pre-elafin
-
-
-
propyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)benzamido)benzoate
-
-
propyl 2-(4-(pivaloyloxy)benzamido)benzoate
-
-
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
-
serpin
-
-
-
serpin LEX032
-
reactive site variant of alpha-1-ACT
-
siRNA
-
less PR3 externalization in the presence of rPLSCR1 siRNA
-
sivelestat
-
-
Soybean trypsin inhibitor
-
-
-
Substituted isocoumarins
-
-
-
trappin
-
80% inhibition, oxidized with N-chlorosuccinimide: 19% inhibition
-
trappin-2
-
pre-elafin
-
Val15-aprotinin
-
[4-[(2,3-diethyl-1,1-dioxido-4-oxo-1,2,3,5-thiatriazolidin-5-yl)methyl]-1H-1,2,3-triazol-1-yl]acetic acid
-
0.00862 mM inhibits by ca. 11%
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cytochalasin B
-
PR3 and CD177 are increased in parallel. Stimulating cells with cytochalasin B in combination with fML, PmPR3- and CD177-negative cells become positive
FcgammaRIIIb
-
acts as a membrane adaptor for PR3
-
fMLP
-
PR3 and CD177 are increased in parallel. Causes a moderate increase. stimulating cells with cytochalasin B in combination with fML, PmPR3- and CD177-negative cells become positive
PMA
-
PR3 and CD177 are increased in parallel. Increases 4.9fold. mPR3- and CD177-negative cells become positive
TNF-alpha
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
6.5
2-aminobenzoyl-VADCADQ-EDDnp
-
-
12.3
2-aminobenzoyl-VADCAQ-EDDnp
-
-
0.0314
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide)
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
0.1731
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ala-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
0.0642
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Arg-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
0.0251
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Asn-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
0.0281
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Asp-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
0.0174
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Gln-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
0.0253
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Glu-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
0.1242
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Gly-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
0.0357
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-His-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
0.2763
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ile-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
0.2436
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Leu-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
0.0729
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Lys-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
1.126
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Phe-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
0.1823
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Pro-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
0.0278
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ser-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
0.0321
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Thr-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
1.274
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Trp-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
0.9823
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Tyr-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
0.3124
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Val-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
3.1
Abz-VADCADRQ-EDDnp
-
-
0.0065
Abz-VADCADY(NO2)
-
37C, pH 7.4, 150 mM NaCl
12
Abz-VADCDDRQ-EDDnp
-
-
3.3
Abz-VADCRDRQ-EDDnp
-
-
2.7
Ac-Ala-Ala-Pro-Ala-p-nitroanilide
-
pH 7.4, 25C
2.8
Ac-Ala-Ala-Pro-Val-p-nitroanilide
-
pH 7.4, 25C
2
Boc-Ala-Ala-Pro-Ala-p-nitroanilide
-
pH 7.4, 25C
1.1 - 1.2
MeOSuc-AAPV-4-nitroanilide
0.61 - 1.5
MeOSuc-AIPM-4-nitroanilide
0.47
MeOSuc-Ala-Ala-Pro-Val-p-nitroanilide
-
pH 7.4, 25C
0.14
MeOSuc-Lys(2-picolinoyl)-Ala-Pro-Val-p-nitroanilide
-
pH 7.4, 25C
0.1
MeOSuc-Lys(2-picolinoyl)-Tyr-Asp-Ala-p-nitroanilide
-
pH 7.4, 25C
0.013
MeOSuc-Lys(2-picolinoyl)-Tyr-Asp-Val-p-nitroanilide
-
pH 7.4, 25C
0.61
Suc-AAA-4-nitroanilide
-
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
3.5
Suc-AAPL-4-nitroanilide
-
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
2.5 - 3.7
Suc-AAPV-4-nitroanilide
0.62
Suc-Ala-Ala-Asp-Val-p-nitroanilide
-
pH 7.4, 25C
0.97
Suc-Ala-Ala-Glu-Val-p-nitroanilide
-
pH 7.4, 25C
0.38
Suc-Ala-Ala-Pro-2-aminobutyric acid-p-nitroanilide
-
pH 7.4, 25C
1.9
Suc-Ala-Ala-Pro-Ala-p-nitroanilide
-
pH 7.4, 25C
0.64
Suc-Ala-Ala-Pro-Ile-p-nitroanilide
-
pH 7.4, 25C
0.5
Suc-Ala-Ala-Pro-Nva-p-nitroanilide
-
pH 7.4, 25C
0.6
Suc-Ala-Ala-Pro-Val-p-nitroanilide
-
pH 7.4, 25C
0.17
Suc-Ala-Tyr-Leu-Val-p-nitroanilide
-
pH 7.4, 25C
0.9
Suc-Leu-Val-Glu-Ala-p-nitroanilide
-
pH 7.4, 25C
0.148
succinyl-Ala-Ala-norvaline-thiobenzyl ester
-
-
0.106
tert-butyloxycarbonyl-Ala-Ala-Ala-thiobenzyl ester
-
-
0.031
tert-butyloxycarbonyl-Ala-Ala-Ile-thiobenzyl ester
-
-
0.061
tert-butyloxycarbonyl-Ala-Ala-Met-thiobenzyl ester
-
-
0.063
tert-butyloxycarbonyl-Ala-Ala-norvaline-thiobenzyl ester
-
-
0.028
tert-butyloxycarbonyl-Ala-Ala-Val-thiobenzyl ester
-
-
additional information
additional information
-
Km values of peptidyl thiobenzyl esters
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5.9
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide)
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
2.1
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ala-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
2.6
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Arg-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
5.3
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Asn-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
4.8
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Asp-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
6.4
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Gln-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
3.3
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Glu-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
3.2
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Gly-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
3.1
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-His-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
1.8
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ile-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
2
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Leu-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
2.5
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Lys-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
1.3
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Phe-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
1.1
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Pro-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
5.1
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ser-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
2.8
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Thr-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
1.3
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Trp-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
1.6
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Tyr-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
4.7
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Val-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
13.2
Ac-Ala-Ala-Pro-Ala-p-nitroanilide
Homo sapiens
-
pH 7.4, 25C
60
Ac-Ala-Ala-Pro-Val-p-nitroanilide
Homo sapiens
-
pH 7.4, 25C
18
Boc-Ala-Ala-Pro-Ala-p-nitroanilide
Homo sapiens
-
pH 7.4, 25C
0.59 - 6.2
MeOSuc-AAPV-4-nitroanilide
0.26 - 7.2
MeOSuc-AIPM-4-nitroanilide
30
MeOSuc-Ala-Ala-Pro-Val-p-nitroanilide
Homo sapiens
-
pH 7.4,25C
138
MeOSuc-Lys(2-picolinoyl)-Ala-Pro-Val-p-nitroanilide
Homo sapiens
-
H 7.4, 25C
192
MeOSuc-Lys(2-picolinoyl)-Tyr-Asp-Ala-p-nitroanilide
Homo sapiens
-
H 7.4, 25C
660
MeOSuc-Lys(2-picolinoyl)-Tyr-Asp-Val-p-nitroanilide
Homo sapiens
-
H 7.4, 25C
0.031
Suc-AAA-4-nitroanilide
Mus musculus
-
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
0.16
Suc-AAPL-4-nitroanilide
Mus musculus
-
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
0.37 - 11.2
Suc-AAPV-4-nitroanilide
84
Suc-Ala-Ala-Asp-Val-p-nitroanilide
Homo sapiens
-
pH 7.4, 25C
60
Suc-Ala-Ala-Glu-Val-p-nitroanilide
Homo sapiens
-
pH 7.4, 25C
30
Suc-Ala-Ala-Pro-2-aminobutyric acid-p-nitroanilide
Homo sapiens
-
pH 7.4, 25C
13.8
Suc-Ala-Ala-Pro-Ala-p-nitroanilide
Homo sapiens
-
pH 7.4, 25C
16.2
Suc-Ala-Ala-Pro-Ile-p-nitroanilide
Homo sapiens
-
pH 7.4, 25C
5.4
Suc-Ala-Ala-Pro-Nva-p-nitroanilide
Homo sapiens
-
pH 7.4, 25C
12
Suc-Ala-Ala-Pro-Val-p-nitroanilide
Homo sapiens
-
pH 7.4, 25C
3 - 6
Suc-Ala-Tyr-Leu-Val-p-nitroanilide
Homo sapiens
-
pH 7.4, 25C
2 - 22.2
Suc-Leu-Val-Glu-Ala-p-nitroanilide
19
Succinyl-Ala-Ala-norvaline thiobenzyl ester
Homo sapiens
-
-
10.1
tert-butyloxycarbonyl-Ala-Ala-Ala thiobenzyl ester
Homo sapiens
-
-
1.9
tert-butyloxycarbonyl-Ala-Ala-Ile thiobenzyl ester
Homo sapiens
-
-
12.2
tert-butyloxycarbonyl-Ala-Ala-Met thiobenzyl ester
Homo sapiens
-
-
63.3
tert-butyloxycarbonyl-Ala-Ala-norvaline thiobenzyl ester
Homo sapiens
-
-
10.4
tert-butyloxycarbonyl-Ala-Ala-Val thiobenzyl ester
Homo sapiens
-
-
additional information
additional information
Homo sapiens
-
turnover numbers of peptidyl thiobenzyl esters
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
188.9
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide)
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
40585
12.2
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ala-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
40587
41.1
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Arg-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
40596
201.2
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Asn-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
40600
170.8
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Asp-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
40599
274.9
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Gln-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
40598
138.2
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Glu-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
40597
25.8
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Gly-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
40586
86.7
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-His-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
40594
6.5
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ile-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
40589
7.2
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Leu-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
40590
34.3
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Lys-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
40595
1.1
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Phe-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
40591
0.5
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Pro-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
40603
183.8
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ser-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
40601
87.3
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Thr-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
40602
0.9
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Trp-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
40593
1.6
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Tyr-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
40592
15.1
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Val-NH2
Homo sapiens
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25C
40588
1500
N-Boc-3-[2-[2-(1'-methyl)pyrrolo]benzoxazol-5-yl]-Ala-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide)
Homo sapiens
-
-
160398
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00000012
elafin
-
0.000025
elafin, oxidized with myeloperoxidase
-
methoxysuccinyl-lysyl-(2-picolinoyl)-Ala-Pro-Val-thiobenzylester as substrate, pH 7.4, 150 mM NaCl, 3 mM 4,4-dithiodipyridine
-
0.000029
elafin, oxidized with N-chlorosuccinimide
-
methoxysuccinyl-lysyl-(2-picolinoyl)-Ala-Pro-Val-thiobenzylester as substrate, pH 7.4, 150 mM NaCl, 3 mM 4,4-dithiodipyridine
-
0.000012
serpin LEX032
-
pH 7.5, 25C
-
0.00000018
trappin
-
methoxysuccinyl-lysyl-(2-picolinoyl)-Ala-Pro-Val-thiobenzylester as substrate, pH 7.4, 150 mM NaCl, 3 mM 4,4-dithiodipyridine
-
0.000035
trappin, oxidized with myeloperoxidase
-
methoxysuccinyl-lysyl-(2-picolinoyl)-Ala-Pro-Val-thiobenzylester as substrate, pH 7.4, 150 mM NaCl, 3 mM 4,4-dithiodipyridine
-
0.00005
trappin, oxidized with N-chlorosuccinimide
-
methoxysuccinyl-lysyl-(2-picolinoyl)-Ala-Pro-Val-thiobenzylester as substrate, pH 7.4, 150 mM NaCl, 3 mM 4,4-dithiodipyridine
-
0.00000018
trappin-2
-
25C, recombinant trappin-2 expressed in Pichia pastoris
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00173
(E)-4-(N-(2-(1-(hydroxyimino)butyl)phenyl)sulfamoyl)phenyl pivalate
Homo sapiens
-
pH 7.4, 30C
0.00022
(E)-4-(N-(2-(1-(hydroxyimino)ethyl)phenyl)sulfamoyl)phenyl pivalate
Homo sapiens
-
pH 7.4, 30C
0.00053
(E)-4-(N-(2-(1-(hydroxyimino)methyl)phenyl)sulfamoyl)phenyl pivalate
Homo sapiens
-
pH 7.4, 30C
0.0025
(E)-4-(N-(2-(1-(hydroxyimino)propyl)phenyl)sulfamoyl)phenyl pivalate
Homo sapiens
-
pH 7.4, 30C
0.00061
(E)-4-(N-(2-(1-(methoxyimino)ethyl)phenyl)sulfamoyl)phenyl pivalate
Homo sapiens
-
pH 7.4, 30C
0.00237
(Z)-4-(N-(2-(1-(methoxyimino)ethyl)phenyl)sulfamoyl)phenyl pivalate
Homo sapiens
-
pH 7.4, 30C
0.00061
2-hydroxyethyl 2-(4-(pivaloyloxy)phenylsulfonamido)benzoate
Homo sapiens
-
pH 7.4, 30C
0.00031
4-(N-(2-(2-hydroxyethylcarbamoyl)phenyl)sulfamoyl)phenyl pivalate
Homo sapiens
-
pH 7.4, 30C
0.01
4-(N-(2-acetylphenyl)sulfamoyl)phenyl 2-methylpropane-2-sulfinate
Homo sapiens
-
pH 7.4, 30C
0.00047
4-(N-(2-acetylphenyl)sulfamoyl)phenyl pivalate
Homo sapiens
-
pH 7.4, 30C
0.00036
4-(N-(2-butyrylphenyl)sulfamoyl)phenyl pivalate
Homo sapiens
-
pH 7.4, 30C
0.01
4-(N-(2-formylphenyl)sulfamoyl)phenyl 2-methylpropane-2-sulfinate
Homo sapiens
-
pH 7.4, 30C
0.00205
4-(N-(2-formylphenyl)sulfamoyl)phenyl pivalate
Homo sapiens
-
pH 7.4, 30C
0.00231
4-(N-(2-pentanoyl phenyl)sulfamoyl)phenyl pivalate
Homo sapiens
-
pH 7.4, 30C
0.00109
4-(N-(2-propionylphenyl)sulfamoyl)phenyl pivalate
Homo sapiens
-
pH 7.4, 30C
740 - 980
Alpha1-antitrypsin
-
3300 - 117000
Eglin c
990 - 1900
elafin
-
0.01
ethyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)benzamido)benzoate
Homo sapiens
-
pH 7.4, 30C
0.00302
ethyl 2-(4-(pivaloyloxy)benzamido)benzoate
Homo sapiens
-
pH 7.4, 30C
0.01
methyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)benzamido)benzoate
Homo sapiens
-
pH 7.4, 30C
0.00494
methyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)phenylsulfonamide)benzoate
Homo sapiens
-
pH 7.4, 30C
0.00205
methyl 2-(4-(pivaloyloxy)benzamido)benzoate
Homo sapiens
-
pH 7.4, 30C
0.01
methyl 2-(4-pivalamidophenylsulfonamido)benzoate
Homo sapiens
-
pH 7.4, 30C
0.01
propyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)benzamido)benzoate
Homo sapiens
-
pH 7.4, 30C
0.00391
propyl 2-(4-(pivaloyloxy)benzamido)benzoate
Homo sapiens
-
pH 7.4, 30C
0.00034
sivelestat
Homo sapiens
-
pH 7.4, 30C
447000
Val15-aprotinin
Mus musculus
-
MeOSuc-AAPV-4-nitroanilide as substrate, 1% Triton X-100 (w/v), 20% dimethylformamide (v/v), pH 8.0, IC50 = 447 M
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
assay methods
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
-
assay at
additional information
-
pI: 9.1
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
the mature PR3 has an inactive conformation in the acidic environment of the azurophilic granules, and becomes active upon translocation to a neutral pH environment
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
-
assay at
37
-
assay at
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.7
-
calculated from amino acid sequence
7.7
-
calculated from amino acid sequence
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
increased PR-3 on the alveolar macrophage surface in usual interstitial pneumonia relative to healthy controls and sarcoidosis subjects
Manually annotated by BRENDA team
-
proteinase 3 is considerably more expressed in bone marrow than in the peripheral blood
Manually annotated by BRENDA team
-
inflamed oral epithelial cell
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
large amounts
Manually annotated by BRENDA team
additional information
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22000
-
3 * 29000 + 1 * 22000, SDS-PAGE
32000
-
recombinant mutant N102Q and N147Q, immunoprecipitation
34000
-
recombinant PR3 wild-type, immunoprecipitation
36000
-
recombinant PR3 wild-type, immunoprecipitation
additional information
-
processing of proteinase 3 in U937 human myelomonocytic cell line: a 35000 MW precursor is converted into a 29000 MW mature form
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
-
1 * 29000, SDS-PAGE
multimer
-
3 * 29000 + 1 * 22000, SDS-PAGE
tetramer
-
crystallography
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Sap3 in a stable complex with pepstatin A and in the absence of an inhibitor, in the presence of Zn2+, to 1.9 and 2.2 A resolution. Inhibitor binding causes active site closure by the movement of a flap segment. Sap3 consists of the S2' binding site becoming channelshaped subsequent to the turn of the loop with residues 129135
-
adopts a fold consisting of two beta-barrels made each of six anti-parallel beta-sheets. Crystallizes as a tetramer, which can be regarded as a dimer of dimers: two monomers in a dimer are oriented so that their active sites face each other, preventing the binding of large substrates. The hole in the middle of the tetramer is lined with hydrophobic residues. Contains four disulfide bridges between cysteine pairs 42-58, 136-201, 168-182 and 191-220. No X-ray structure of PR3 with a substrate in its active site available
-
crystal structure of recombinant PR3. Overall fold consists of two beta-barrel domains. PR3 structure includes a disaccharide unit covalently attached to Asn159. PR3 substrate binding sites at S4 to S3'
-
molecular dynamics simulations of PR3 anchored at three different phospholipid bilayers: dimyristoylphosphatidylcholine DMPC and dimyristoylphosphatidylglycerol DMPG, and an equimolar mixture of DMPC/DMPG. Basic residues R177, R186A, R186B, K187 and R222 interact via hydrogen bonds with the lipid headgroups to stabilize PR3 at the interfacial membrane region. Hydrophobic amino acids V163, F165, F166, I217, L223, and F224 insert into the hydrophobic core below the carbonyl groups of the bilayers and aromatic amino acids F165, F192, F215, W218, F224, and F227 contribute electrostatic interaction via cation-pi interactions with the choline groups of DMPC. PR3 presents all the characteristics of a peripheral membrane protein with an ability to bind negative phospholipids. The catalytic triad remains unperturbed by the presence of the membrane, the ligand binding sites are located in close proximity to the membrane and amino acids K99 and I217 interact significantly with the lipids
-
to 2.2 A resolution
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
glycosylation at Asn-147, but not at Asn-102, is critical for thermal stability
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
6 x His-tagged proPR3 purified using affinity chromatography
by anion-exchange chromatography and gel filtration
-
by nickel-chelating affinity chromatography
-
more than 95% pure
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
DELTAAE-PR3(S176A)-His expressed in HEK-293 cells
-
expressed in insect cells
-
expressed in Pichia pastoris
-
expressed in Sf-9 insect cells, HEK-293, HMC-1, RBL-1 and CHO cells. Expression of PR3 as a completely denatured and aggregated protein in Escherichia coli. Expression in Pichia pastoris or Saccharomyces cerevisiae
-
expression in COS cell
-
expression in HMC-1 cells and 293 cells
expression in RBL cell
-
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
-
expression using baculoviral system
-
full-length cDNA amplified, enterokinase cleavage site (DDDDK) introduced at the N terminus of PR3. PCR product digested with PmlI/AgeI and cloned into the reading frame of the S-tag, resulting in construct pcDNA5/FRT/hPR3-H6. Human/gibbon chimeras performed by digestion of pcDNA5/FRT/PR3-H6 with BlpI and AgeI and exchange of the respective cDNA segments. Expression in Flp-in HEK293 cells
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granulocyte cDNA amplified, PCR fragment reamplified and cloned into pcDNA5/FRT. Human/gibbon chimeras performed by digestion of pcDNA5/FRT/PR3-H6 with BlpI and AgeI and exchange of the respective cDNA segments. Chemically synthesized 390-bp human PR3 fragment digested with PmlI/BlpI and cloned into the same sites of the pcDNA5/FRT/gPR3-H6 plasmid to reconstruct the human CLB12.8 epitope in gibbon PR3 (gibbon proteinase 3 variant 1). A further modification of this variant by replacing the A116 to Q119 tetrapeptide with the respective opossum residues Q-V-A-S. To this end, a DNA fragment chemically synthesized, digested with BlpI and BstEII, and subcloned into the same sites of the gPR3v1 plasmid. The two glycosylation sites Asn113 and Asn159 mutated to lysine residues in the gibbon proteinase 3 variant 2. Expression in Flp-in HEK293 cells
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mast cell lines transfected with PR3
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mice immunized with recombinant or synthetic human complementary PR3
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myeloblastin and proteinase 3 are encoded by a single mRNA
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overexpression of active PR3 and its inactive mutant in HEK-293T cells
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RBL-2H3 rat mast-cell line stably transfected with PR3 or its inactive mutant S203A
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recombinant PR3 expressed in HMC1 cells
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recombinant PR3 expressed in RBL cells
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recombinant PR3 wild-type and recombinant PR3 glycosylation variants expressed in HMC-1 cells
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recombinant PRTN3 protein with an amino-terminal histidine tag produced in SF-9 insect cells by use of a baculovirus expression system
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
activation with the calcium ionophore A23187 to optimize membrane-bound Pr3 exposure at the cell surface, whereby Pr3 activity increases by 5-20fold. Resting neutrophils have a genetically determined distribution of the protease that results in a bimodal membrane-bound Pr3 expression
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expression of membrane PR3 and CD177 on the same subset of neutrophils
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in patients with anti-neutrophil cytoplasmic antibodies-associated systemic vasculitis, increased mRNA levels of both PR3 and CD177 are found, which do not correlate with the proportion of double-positive cells
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increased percentages of mPR3-expressing neutrophils in patients with ANCA-associated systemic vasculitis (median 67%, range 16-100%) and patients with systemic lupus erythematosus (median 80%, range 25-100%), but not in patients with rheumatoid arthritis (median 61%, range 0-100%). Correlation of CD177 expression with PR3 expression on primed neutrophils. After priming with tumor necrosis factor alpha, neutrophils remain negative for CD177 while PR3 expression is induced. Expression of PR3 on the neutrophil surface can be independent of CD177 expression. Among the patients with PR3 ANCA-associated vasculitis, patients treated with cyclophosphamide or prednisolone have higher percentages of CD177-expressing neutrophils than do patients who have not received these treatments
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size of the membrane-bound PR3 high expressing neutrophils ranges from 0% to 100% of the total number of neutrophils in a healthy population and remains strikingly constant within one individual over time. Percentage of membrane-bound PR3 expressing neutrophils is genetically determined. Elevated expression levels of membrane-bound PR3 in Wegener's granulomatosis, PR3-anti-neutrophil cytoplasmic autoantibodies associated vasculitis and other chronic inflammatory diseases. TNF-alpha may translocate PR3 to the plasma membrane and raise the expression level up to 2- to 3folds of that on resting neutrophils. IL-8, TGF-beta and GM-CSF upregulate membrane PR3 expression on neutrophils. CD177 is the receptor of membrane-bound PR3 and mediates PR3 expression on the neutrophil membrane
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
F180A/F181A
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mutant is still able to display membrane PR3 after degranulation, with similar fluorescence intensity as wild-type
F180A/F181A/L228A/F229A
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contrary to wild-type, membrane anchorage is abrogated in mutant. Mutant is still able to cleave the synthetic substrate Boc-Ala-Pro-Val in cell lysates, but fails to cleave extracellular fibronectin, is not externalized after apoptosis and does not impair macrophage phagocytosis of apoptotic cells, does not promote myeloid cell proliferation and fails to cleave p21/waf1
F180A/L228A/F229A
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mutant is still able to display membrane PR3 after degranulation, with similar fluorescence intensity as wild-type
L228A
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mutant is still able to display membrane PR3 after degranulation, with similar fluorescence intensity as wild-type
L228A/F229A
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mutant is still able to display membrane PR3 after degranulation, with similar fluorescence intensity as wild-type
N102Q
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glycosylation deficient recombinant PR3 mutant, hydrolytic activity like recombinant PR3-wild-type. N-terminal processing is delayed
N102Q/N147Q
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glycosylation deficient recombinant PR3 mutant, reduction in hydrolytic activity in relation to recombinant PR3-wild-type. Reduction in hydrolytic activity is more pronounced than the reduction induced by deglycosylation of purified neutrophil PR3. N-terminal processing is delayed
N147Q
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glycosylation deficient recombinant PR3 mutant, is processed like recombinant PR3-wild-type
R193A/R194A/K195A
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mutant does not affect membrane expression
R193A/R194A/K195A/R227A
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contrary to wild-type, membrane anchorage is abrogated in mutant
R194A/K195A/R227A
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mutant does not affect membrane expression
S176A
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substitution of the active centre
S195A
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site-directed mutagenesis, cDNA construction of a catalytically inactive active site enyzme mutant lacking the codons for the N-terminal activation dipeptide, DELTAPR3ctp-S195A
V35M/S38AN/I38BP/Q74R/N113K/N159K/119-122QVAS
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results in the gibbon proteinase 3 variant 2. Is no longer able to interact with the mouse antibodies 4A5 and WGM2, but retains its binding to CLB12.8
V35M/S38AN/L39BP/Q74R
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results in the gibbon proteinase 3 variant 1. The binding site for mouse antibody CLB12.8, but not that for MCPR3-2, is reconstituted. Binds also to mouse antibody 6A6. Like MCPR3-2, WGM3 binds neither to gibbon PR3 nor to the humanized gibbon proteinase 3 variant 1
additional information
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catalytically inactive Ser195-substituted PR3 variant, eliminates quality check of the antigen preperation. Recombinant PR3 variants which only carry a single antigenic region on its surface may be used to neutralize or eliminate circulating anti-neutrophil cytoplasmic antibodies (ANCA) in patients without triggering immune complex-mediated type III reactions
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
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knowledge of the protonation states of the ionizable residues in an enzyme like PR3 is a prerequisite to an accurate description of its structure and mechanism
diagnostics
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anti-neutrophil cytoplasmic antibodies with proteinase 3 specificity are a useful laboratory biomarker for the diagnosis of granulomatosis with polyangiitis, i.e.Wegener's granulomatosis
drug development
medicine
additional information
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design of potent and highly specific substrates of proteinase 3 and other proteinases optimized in the prime site region