Information on EC 3.4.21.76 - Myeloblastin

metabolism

physiological function

18 entries

additional information

-

proteinase 3 is an abundant serine protease with high similarity to neutrophil elastase

(7-methoxycoumarin-4-yl)acetyl-Ala-Ala-Ala-Ala-Lys-Gly-Asp-Dpa-NH2 + H2O

?

-

-

?

(7-methoxycoumarin-4-yl)acetyl-Ala-Ala-Pro-Leu-Lys-Gly-Asp-Dpa-NH2 + H2O

?

-

-

?

(7-methoxycoumarin-4-yl)acetyl-Ala-Ala-Pro-Val-Lys-Gly-Asp-Dpa-NH2 + H2O

?

-

-

?

(7-methoxycoumarin-4-yl)acetyl-Lys(2-picolinoyl)-Tyr-Asp-Ala-Lys-Gly-Asp-Dpa-NH2 + H2O

?

-

-

?

(7-methoxycoumarin-4-yl)acetyl-Lys(2-picolinoyl)-Tyr-Asp-Ile-Lys-Gly-Asp-Dpa-NH2 + H2O

?

-

-

?

(7-methoxycoumarin-4-yl)acetyl-Lys(2-picolinoyl)-Val-Glu-Ala-Lys-Gly-Asp-Dpa-NH2 + H2O

?

-

-

?

(VGVAPG)2V + H2O

?

-

pH 8.6, room temperature

-

?

(VGVAPG)3V + H2O

?

-

pH 8.6, room temperature

-

?

2-aminobenzoyl-APEEIM(o)DRQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O

?

-

-

?

2-aminobenzoyl-APEEIMDRQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O

?

-

-

?

2-aminobenzoyl-APEEIMMDRQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O

?

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-

?

2-aminobenzoyl-EAIPMSIPPEVKFNKQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O

?

-

-

?

2-aminobenzoyl-EAIPMSIPQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O

?

-

-

?

2-aminobenzoyl-GIATFCM(o)LM(o)PEQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O

?

-

-

?

2-aminobenzoyl-GIATFCMLMPEQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O

?

-

-

?

2-aminobenzoyl-IVSARMAPEEIIMDRQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O

?

-

-

?

2-aminobenzoyl-MMRCAQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O

?

-

-

?

2-aminobenzoyl-TFCM(o)LEQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O

?

-

-

?

2-aminobenzoyl-TFCMLEQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O

?

-

-

?

2-aminobenzoyl-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide) + H2O

?

-

-

?

2-aminobenzoyl-VADCAQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O

?

-

-

?

2-aminobenzoyl-VAECCQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O

?

-

-

?

2-aminobenzoyl-VSARQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O

?

-

-

?

5-TAMRA-VADnVADYQ-DAP(CF) + H2O

?

-

a fluorescence resonance energy transfer, FRET, substrate. The reaction is inhibited by antibody MCPR3-7 binding

-

?

5-TAMRA-VADnVRDYQ-diaminopropionyl-fluorescein + H2O

?

-

fluorogenic substrate

-

?

Abz-APEEIMDDQ-ethylene diamine 2,4 dinitrophenyl + H2O

?

37°C, pH 7.4, 150 mM NaCl, kcat/KM = 2.5/mM/s

-

?

Abz-APEEIMDQQ-ethylene diamine 2,4 dinitrophenyl + H2O

?

37°C, pH 7.4, 150 mM NaCl, kcat/KM = 2/mM/s

-

?

Abz-APEEIMDRQ-ethylene diamine 2,4 dinitrophenyl + H2O

?

37°C, pH 7.4, 150 mM NaCl, kcat/KM = 14.6/mM/s

-

?

Abz-APEEIMDRY-ethylene diamine 2,4 dinitrophenyl + H2O

?

37°C, pH 7.4, 150 mM NaCl, kcat/KM = lower than 1/mM/s

-

?

Abz-APEEIMDRYQ-ethylene diamine 2,4 dinitrophenyl + H2O

?

37°C, pH 7.4, 150 mM NaCl, kcat/KM = 3.2/mM/s

-

?

Abz-APEEIMDYQ-ethylene diamine 2,4 dinitrophenyl + H2O

?

37°C, pH 7.4, 150 mM NaCl, kcat/KM = 2.6/mM/s

-

?

Abz-APEEIMPRQ-ethylene diamine 2,4 dinitrophenyl + H2O

?

37°C, pH 7.4, 150 mM NaCl, kcat/KM = lower than 1/mM/s

-

?

Abz-APEEIMRRQ-ethylene diamine 2,4 dinitrophenyl + H2O

?

37°C, pH 7.4, 150 mM NaCl, kcat/KM = lower than 1/mM/s

-

?

Abz-GIATDCRDRPEQ-EDDnp + H2O

?

-

-

?

Abz-GIATFCDLMPEQ-EDDnp + H2O

?

-

-

?

Abz-GIATFCMKMPEQ-EDDnp + H2O

?

-

-

?

Abz-GIATFCMLMPEQ-EDDnp + H2O

?

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-

?

Abz-GIATFCRLMPEQ-EDDnp + H2O

?

-

-

?

Abz-GRATFCMLMPEQ-EDDnp + H2O

?

-

-

?

Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide) + H2O

Abz-Tyr-Tyr-Abu + 5-amino-2-nitrobenzamide

-

-

?

Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ala-NH2 + H2O

Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Ala-NH2

-

-

?

Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Arg-NH2 + H2O

Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Arg-NH2

-

-

?

Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Asn-NH2 + H2O

Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Asn-NH2

-

-

?

Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Asp-NH2 + H2O

Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Asp-NH2

-

-

?

Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Gln-NH2 + H2O

Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Gln-NH2

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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

-

-

?

Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Gly-NH2 + H2O

Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Gly-NH2

-

-

?

Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-His-NH2 + H2O

Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-His-NH2

-

-

?

Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ile-NH2 + H2O

Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Ile-NH2

-

-

?

Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Leu-NH2 + H2O

Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Leu-NH2

-

-

?

Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Lys-NH2 + H2O

Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Lys-NH2

-

-

?

Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Phe-NH2 + H2O

Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Phe-NH2

-

-

?

Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Pro-NH2 + H2O

Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Pro-NH2

-

-

?

Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ser-NH2 + H2O

Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Ser-NH2

-

-

?

Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Thr-NH2 + H2O

Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Thr-NH2

-

-

?

Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Trp-NH2 + H2O

Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Trp-NH2

-

-

?

Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Tyr-NH2 + H2O

Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Tyr-NH2

-

-

?

Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Val-NH2 + H2O

Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Val-NH2

-

-

?

Abz-Tyr-Tyr-Abu-ANB-NH2 + H2O

?

-

a fluorescence resonance energy transfer, FRET, substrate. The reaction is inhibited by antibody MCPR3-7 binding

-

?

Abz-VADCADQ-(2,4-dinitrophenyl)ethylenediamine + H2O

?

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-

?

Abz-VADCADQ-EDDnp + H2O

?

-

-

?

Abz-VADCADQ-ethylene diamine 2,4 dinitrophenyl + H2O

?

Abz-VADCADQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O

?

-

-

?

Abz-VADCADRQ-EDDnp + H2O

Abz-VADCA + DRQ-EDDnp

-

-

?

Abz-VADCADRY(NO2) + H2O

?

37°C, pH 7.4, 150 mM NaCl, kcat/KM = 651/mM/s

-

?

Abz-VADCADY(NO2) + H2O

?

37°C, pH 7.4, 150 mM NaCl, kcat/KM = 630/mM/s

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?

Abz-VADCAPY(NO2) + H2O

?

37°C, pH 7.4, 150 mM NaCl, kcat/KM = lower than 1/mM/s

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?

Abz-VADCAQ-EDDnp + H2O

?

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-

?

Abz-VADCAQ-ethylene diamine 2,4 dinitrophenyl + H2O

?

37°C, pH 7.4, 150 mM NaCl, kcat/KM = 292/mM/s

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?

Abz-VADCARY(NO2) + H2O

?

37°C, pH 7.4, 150 mM NaCl, kcat/KM = 3.8/mM/s

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?

Abz-VADCAY(NO2) + H2O

?

37°C, pH 7.4, 150 mM NaCl, kcat/KM = 10.9/mM/s

-

?

Abz-VADCDDRQ-EDDnp + H2O

Abz-VADCD + DRQ-EDDnp

-

-

?

Abz-VADCRDRQ-EDDnp + H2O

Abz-VADCR + DRQ-EDDnp

Abz-VADnVADRQ-EDDnp + H2O

Abz-VADnVA + DRQ-EDDnp

-

-

?

Abz-VADnVADYQ-EDDnp + H2O

?

-

-

?

Abz-VADnVRDRQ-EDDnp + H2O

Abz-VADnVR + DRQ-EDDnp

-

-

?

Abz-VADnVRDYQ-EDDnp + H2O

?

-

-

?

Abz-VADVKDRQ-EDDnp + H2O

Abz-VADVK + DRQ-EDDnp

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-

?

Abz-VADVKDRQ-ethylene diamine 2,4 dinitrophenyl + H2O

?

-

665985

-

?

Abz-Val-Ala-Asp-Nvl-Ala-Asp-Arg-Gln-N-(2,4-dinitrophenyl)ethylenediamine + H2O

?

-

709030

-

?

Abz-VARCRDRQ-EDDnp + H2O

Abz-VARCR + DRQ-EDDnp

-

-

?

Ac-Ala-Ala-Pro-Ala-p-nitroanilide + H2O

?

-

-

?

Ac-Ala-Ala-Pro-Val-p-nitroanilide + H2O

?

-

-

?

Ahx-PYFA-4-nitroanilide + H2O

?

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the reaction is inhibited by antibody MCPR3-7 binding

-

?

annexin 1 + H2O

?

-

proteinase 3 is the main enzyme responsible for cleavage in the N terminus region of the protein

687618

-

?

APG(VGVAPG)2V + H2O

?

-

pH 8.6, room temperature

-

?

azocasein + H2O

fragments of azocasein

-

-

BID + H2O

?

-

37°C, Bid = BH3 interacting domain death agonist

666199

-

?

Boc-Ala-Ala-Nva-SBzl + H2O

?

-

652675

-

652675

?

Boc-Ala-Ala-Nva-thiobenzyl ester + H2O

?

-

-

?

Boc-Ala-Ala-Nva-thiobenzylester + H2O

?

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pH 8.6, room temperature

-

?

Boc-Ala-Ala-Pro-Ala-p-nitroanilide + H2O

?

-

-

?

Boc-Ala-ONp + H2O

?

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the reaction is not inhibited by antibody MCPR3-7 binding

-

?

Boc-Ala-Pro-Nva-4-chloro-thiobenzyl ester + H2O

?

Boc-Ala-Pro-Nva-SBzl + H2O

?

-

-

?

Boc-Ala-Pro-Nva-thiobenzylester + H2O

?

Boc-Ala-Pro-nVal-SBzl + H2O

?

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the reaction is not inhibited by antibody MCPR3-7 binding

-

?

casein + H2O

?

Candida albicans

-

689931

-

?

Collagen type IV + H2O

Hydrolyzed collagen type IV

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no or minimal activity against interstitial collagens type I and III

-

DRDAVDRDID + H2O

?

-

-

?

DVARVKDRQEG + H2O

?

-

-

?

Elastin + H2O

Hydrolyzed elastin

endothelial cell protein C receptor + H2O

?

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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 18.5–102 nanomol)

688708

-

?

Fibronectin + H2O

Hydrolyzed fibronectin

-

-

For-Ala-Ala-Pro-Abu-SBzl + H2O

?

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the reaction is partly inhibited by antibody MCPR3-7 binding

-

?

FRET + H2O

?

-

-

?

GDVAVYEEN + H2O

?

-

-

?

Hemoglobin + H2O

Hydrolyzed hemoglobin

-

-

IL-18 + H2O

?

-

-

?

IL-1beta + H2O

?

-

-

?

IL-32 + H2O

?

kininogen + H2O

?

-

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

709349

-

?

laminin + H2O

fragments of laminin

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-

Mca-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide) + H2O

?

-

-

?

MeO-Suc-Ala-Ala-Pro-Val-4-nitroanilide + H2O

MeO-Suc-Ala-Ala-Pro-Val + 4-nitroaniline

-

664451

-

?

MeO-Suc-Lys-(pico)-Ala-Pro-Val-thiobenzylester + H2O

?

-

25°C

664822

-

?

MeOSuc-AAPV-4-nitroanilide + H2O

MeOSuc-AAPV + 4-nitroaniline

MeOSuc-AIPM-4-nitroanilide + H2O

MeOSuc-AIPM + 4-nitroaniline

MeOSuc-Ala-Ala-Pro-Val-p-nitroanilide + H2O

?

-

-

?

MeOSuc-Lys(2-picolinoyl)-Ala-Pro-Val-p-nitroanilide + H2O

?

-

-

?

MeOSuc-Lys(2-picolinoyl)-Tyr-Asp-Ala-p-nitroanilide + H2O

?

-

-

?

MeOSuc-Lys(2-picolinoyl)-Tyr-Asp-Val-p-nitroanilide + H2O

?

-

-

?

methoxysuccinyl-lysyl-(2-picolinoyl)-Ala-Pro-Val-p-nitroanilide + H2O

?

-

pH 7.4, 150 mM NaCl

-

?

methoxysuccinyl-lysyl-(2-picolinoyl)-Ala-Pro-Val-thiobenzylester + H2O

?

-

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

?

-

-

?

N-Boc-3-[2-(2'-methoxy-4'-dimethylaminophenyl)benzoxazol-5-yl]-Ala-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide) + H2O

?

-

-

?

N-Boc-3-[2-(2-quinolinyl)benzoxazol-5-yl]-Ala-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide) + H2O

?

-

-

?

N-Boc-3-[2-[2-(1'-methyl)pyrrolo]benzoxazol-5-yl]-Ala-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide) + H2O

?

-

is the most efficient PR3 substrate

-

?

N-Boc-Ala-o-nitrophenol + H2O

?

-

37°C, pH 7.4

-

?

N-methoxysuccinyl-Ala-Ala-Pro-Val-pNA + H2O

?

-

-

?

N-t-Boc-L-alanine-p-nitrophenyl-ester + H2O

?

-

651049

-

651049

?

NF-kappaB + H2O

?

-

-

?

NFkappaB + H2O

?

-

-

?

nuclear factor-kappaB + H2O

?

-

666199

-

?

oxidized insulin B chain + H2O

?

p21 + H2O

?

p21 protein + H2O

?

PAR-2 + H2O

?

-

PAR-2 = protease-activated receptor 2

664451

-

?

Peptidyl thiobenzyl ester + H2O

?

-

the preferred P1 residue is a small hydrophobic amino acid such as aminobutyric acid, norvaline, valine or alanine, in decreasing order of preference

29720

-

pro-TNFalpha + H2O

?

-

-

?

procaspase 3 + H2O

?

-

PR3 can cleave membrane-associated procaspase 3 into a 22 kDa fragment

-

?

procaspase-3 + H2O

?

proIL-1beta + H2O

active IL-1beta + ?

-

is processed by PR3 or caspase 1

707322

-

?

protease-activated receptor-2

?

-

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)

686192

-

?

protease-activated receptor-2 + H2O

?

-

683193, 684453

-

?

RDVARCRDRQEG + H2O

?

-

-

?

RDVARCRDRQQG + H2O

?

-

-

?

Suc-AAA-4-nitroanilide + H2O

Suc-AAA + 4-nitroaniline

Suc-AAPL-4-nitroanilide + H2O

Suc-AAPL + 4-nitroaniline

Suc-AAPV-4-nitroanilide + H2O

Suc-AAPV + 4-nitroaniline

Suc-Ala-Ala-Asp-Val-p-nitroanilide + H2O

?

-

-

?

Suc-Ala-Ala-Glu-Val-p-nitroanilide + H2O

?

-

-

?

Suc-Ala-Ala-Pro-2-aminobutyric acid-p-nitroanilide + H2O

?

-

-

?

Suc-Ala-Ala-Pro-Ala-p-nitroanilide + H2O

?

-

-

?

Suc-Ala-Ala-Pro-Ile-p-nitroanilide + H2O

?

-

-

?

Suc-Ala-Ala-Pro-Nva-p-nitroanilide + H2O

?

-

-

?

Suc-Ala-Ala-Pro-Val-p-nitroanilide + H2O

?

-

-

?

Suc-Ala-Tyr-Leu-Val-p-nitroanilide + H2O

?

-

-

?

Suc-Ala4-p-nitroanilide + H2O

?

-

-

?

Suc-Leu-Val-Glu-Ala-p-nitroanilide + H2O

?

-

-

?

Succinyl-Ala-Ala-norvaline thiobenzyl ester + H2O

?

-

-

surfactant protein D + H2O

?

Tert-Butyloxycarbonyl-Ala-Ala-Ala thiobenzyl ester + H2O

?

-

-

Tert-Butyloxycarbonyl-Ala-Ala-Ile thiobenzyl ester + H2O

?

-

-

Tert-Butyloxycarbonyl-Ala-Ala-Met thiobenzyl ester + H2O

?

-

-

Tert-Butyloxycarbonyl-Ala-Ala-norvaline thiobenzyl ester + H2O

?

-

best substrate

29717, 29725

-

Tert-Butyloxycarbonyl-Ala-Ala-Val thiobenzyl ester + H2O

?

-

-

TNF-alpha + H2O

?

-

-

?

tumour necrosis factor-alpha + H2O

?

-

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)

697411

-

?

VADVKDR + H2O

?

Val-Ala-Asp-Val-Lys-Asp-Arg + H2O

?

-

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

709688

-

VARVRDR + H2O

?

Vitronectin + H2O

Hydrolyzed vitronectin

-

-

additional information

?

-

16 entries

additional information

?

-

(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

732316

alpha-1-Proteinase inhibitor

-

inhibits the enzyme, inhibition is implicated by anti-neutrophil cytoplasmic antibodies with proteinase 3 specificity

-

alpha-1-proteinase inhibitor serpin

-

651049

-

alpha1-antitrypsin

7 entries

-

alpha1-PI

-

-

alpha1-protease inhibitor

4 entries

-

alpha1-proteinase

-

does not inhibit when PR3 is bound to the outer cell surface of neutrophils

-

Alpha1-proteinase inhibitor

-

alpha2-Macroglobulin

-

29719, 29721, 29722, 683193

-

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

709349

-

benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone

Chloromethylketones

-

DFP

-

diisopropyl fluorophosphate

-

diisopropylfluorophosphate

-

irreversible inhibition

666199

Eglin c

elafin

7 entries

-

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

-

665647

phenylmethylsulfonyl fluoride

-

Phenylmethylsulphonylfluoride

-

664451

phosphatidylinositol-specific phospholipase C

-

687927

-

PI-1

-

-

PMSF

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

649534

-

siRNA

-

less PR3 externalization in the presence of rPLSCR1 siRNA

685785

-

sivelestat

-

SLPI

Soybean trypsin inhibitor

-

-

Substituted isocoumarins

-

-

trappin

-

80% inhibition, oxidized with N-chlorosuccinimide: 19% inhibition

-

trappin-2

-

pre-elafin

664822

-

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

10 entries

-

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

688215

FcgammaRIIIb

-

acts as a membrane adaptor for PR3

687927

-

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

688215

PMA

-

PR3 and CD177 are increased in parallel. Increases 4.9fold. mPR3- and CD177-negative cells become positive

688215

TNF-alpha

-

additional information

4 entries

-

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 25°C

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 25°C

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 25°C

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 25°C

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 25°C

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 25°C

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 25°C

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 25°C

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 25°C

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 25°C

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 25°C

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 25°C

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 25°C

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 25°C

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 25°C

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 25°C

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 25°C

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 25°C

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 25°C

3.1

Abz-VADCADRQ-EDDnp

-

0.0065

Abz-VADCADY(NO2)

-

37°C, 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, 25°C

2.8

Ac-Ala-Ala-Pro-Val-p-nitroanilide

-

pH 7.4, 25°C

2

Boc-Ala-Ala-Pro-Ala-p-nitroanilide

-

pH 7.4, 25°C

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, 25°C

0.14

MeOSuc-Lys(2-picolinoyl)-Ala-Pro-Val-p-nitroanilide

-

pH 7.4, 25°C

0.1

MeOSuc-Lys(2-picolinoyl)-Tyr-Asp-Ala-p-nitroanilide

-

pH 7.4, 25°C

0.013

MeOSuc-Lys(2-picolinoyl)-Tyr-Asp-Val-p-nitroanilide

-

pH 7.4, 25°C

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, 25°C

0.97

Suc-Ala-Ala-Glu-Val-p-nitroanilide

-

pH 7.4, 25°C

0.38

Suc-Ala-Ala-Pro-2-aminobutyric acid-p-nitroanilide

-

pH 7.4, 25°C

1.9

Suc-Ala-Ala-Pro-Ala-p-nitroanilide

-

pH 7.4, 25°C

0.64

Suc-Ala-Ala-Pro-Ile-p-nitroanilide

-

pH 7.4, 25°C

0.5

Suc-Ala-Ala-Pro-Nva-p-nitroanilide

-

pH 7.4, 25°C

0.6

Suc-Ala-Ala-Pro-Val-p-nitroanilide

-

pH 7.4, 25°C

0.17

Suc-Ala-Tyr-Leu-Val-p-nitroanilide

-

pH 7.4, 25°C

0.9

Suc-Leu-Val-Glu-Ala-p-nitroanilide

-

pH 7.4, 25°C

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

-

Km values of peptidyl thiobenzyl esters

29720

-

5.9

Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide)

-

in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C

2.1

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 25°C

2.6

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 25°C

5.3

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 25°C

4.8

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 25°C

6.4

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 25°C

3.3

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 25°C

3.2

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 25°C

3.1

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 25°C

1.8

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 25°C

2

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 25°C

2.5

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 25°C

1.3

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 25°C

1.1

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 25°C

5.1

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 25°C

2.8

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 25°C

1.3

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 25°C

1.6

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 25°C

4.7

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 25°C

13.2

Ac-Ala-Ala-Pro-Ala-p-nitroanilide

-

pH 7.4, 25°C

60

Ac-Ala-Ala-Pro-Val-p-nitroanilide

-

pH 7.4, 25°C

18

Boc-Ala-Ala-Pro-Ala-p-nitroanilide

-

pH 7.4, 25°C

0.59 - 6.2

MeOSuc-AAPV-4-nitroanilide

0.26 - 7.2

MeOSuc-AIPM-4-nitroanilide

30

MeOSuc-Ala-Ala-Pro-Val-p-nitroanilide

-

pH 7.4,25°C

138

MeOSuc-Lys(2-picolinoyl)-Ala-Pro-Val-p-nitroanilide

-

H 7.4, 25°C

192

MeOSuc-Lys(2-picolinoyl)-Tyr-Asp-Ala-p-nitroanilide

-

H 7.4, 25°C

660

MeOSuc-Lys(2-picolinoyl)-Tyr-Asp-Val-p-nitroanilide

-

H 7.4, 25°C

0.031

Suc-AAA-4-nitroanilide

-

52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0

0.16

Suc-AAPL-4-nitroanilide

-

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

-

pH 7.4, 25°C

60

Suc-Ala-Ala-Glu-Val-p-nitroanilide

-

pH 7.4, 25°C

30

Suc-Ala-Ala-Pro-2-aminobutyric acid-p-nitroanilide

-

pH 7.4, 25°C

13.8

Suc-Ala-Ala-Pro-Ala-p-nitroanilide

-

pH 7.4, 25°C

16.2

Suc-Ala-Ala-Pro-Ile-p-nitroanilide

-

pH 7.4, 25°C

5.4

Suc-Ala-Ala-Pro-Nva-p-nitroanilide

-

pH 7.4, 25°C

12

Suc-Ala-Ala-Pro-Val-p-nitroanilide

-

pH 7.4, 25°C

3 - 6

Suc-Ala-Tyr-Leu-Val-p-nitroanilide

-

pH 7.4, 25°C

2 - 22.2

Suc-Leu-Val-Glu-Ala-p-nitroanilide

19

Succinyl-Ala-Ala-norvaline thiobenzyl ester

-

10.1

tert-butyloxycarbonyl-Ala-Ala-Ala thiobenzyl ester

-

1.9

tert-butyloxycarbonyl-Ala-Ala-Ile thiobenzyl ester

-

12.2

tert-butyloxycarbonyl-Ala-Ala-Met thiobenzyl ester

-

63.3

tert-butyloxycarbonyl-Ala-Ala-norvaline thiobenzyl ester

-

10.4

tert-butyloxycarbonyl-Ala-Ala-Val thiobenzyl ester

-

additional information

-

turnover numbers of peptidyl thiobenzyl esters

29720

-

188.9

Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide)

-

in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C

12.2

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 25°C

41.1

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 25°C

201.2

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 25°C

170.8

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 25°C

274.9

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 25°C

138.2

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 25°C

25.8

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 25°C

86.7

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 25°C

6.5

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 25°C

7.2

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 25°C

34.3

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 25°C

1.1

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 25°C

0.5

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 25°C

183.8

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 25°C

87.3

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 25°C

0.9

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 25°C

1.6

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 25°C

15.1

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 25°C

1500

N-Boc-3-[2-[2-(1'-methyl)pyrrolo]benzoxazol-5-yl]-Ala-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide)

-

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, 25°C

649534

-

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

-

25°C, recombinant trappin-2 expressed in Pichia pastoris

664822

-

0.00173

(E)-4-(N-(2-(1-(hydroxyimino)butyl)phenyl)sulfamoyl)phenyl pivalate

Homo sapiens;

-

pH 7.4, 30°C

0.00022

(E)-4-(N-(2-(1-(hydroxyimino)ethyl)phenyl)sulfamoyl)phenyl pivalate

Homo sapiens;

-

pH 7.4, 30°C

0.00053

(E)-4-(N-(2-(1-(hydroxyimino)methyl)phenyl)sulfamoyl)phenyl pivalate

Homo sapiens;

-

pH 7.4, 30°C

0.0025

(E)-4-(N-(2-(1-(hydroxyimino)propyl)phenyl)sulfamoyl)phenyl pivalate

Homo sapiens;

-

pH 7.4, 30°C

0.00061

(E)-4-(N-(2-(1-(methoxyimino)ethyl)phenyl)sulfamoyl)phenyl pivalate

Homo sapiens;

-

pH 7.4, 30°C

0.00237

(Z)-4-(N-(2-(1-(methoxyimino)ethyl)phenyl)sulfamoyl)phenyl pivalate

Homo sapiens;

-

pH 7.4, 30°C

0.00061

2-hydroxyethyl 2-(4-(pivaloyloxy)phenylsulfonamido)benzoate

Homo sapiens;

-

pH 7.4, 30°C

0.00031

4-(N-(2-(2-hydroxyethylcarbamoyl)phenyl)sulfamoyl)phenyl pivalate

Homo sapiens;

-

pH 7.4, 30°C

0.01

4-(N-(2-acetylphenyl)sulfamoyl)phenyl 2-methylpropane-2-sulfinate

Homo sapiens;

-

pH 7.4, 30°C

0.00047

4-(N-(2-acetylphenyl)sulfamoyl)phenyl pivalate

Homo sapiens;

-

pH 7.4, 30°C

0.00036

4-(N-(2-butyrylphenyl)sulfamoyl)phenyl pivalate

Homo sapiens;

-

pH 7.4, 30°C

0.01

4-(N-(2-formylphenyl)sulfamoyl)phenyl 2-methylpropane-2-sulfinate

Homo sapiens;

-

pH 7.4, 30°C

0.00205

4-(N-(2-formylphenyl)sulfamoyl)phenyl pivalate

Homo sapiens;

-

pH 7.4, 30°C

0.00231

4-(N-(2-pentanoyl phenyl)sulfamoyl)phenyl pivalate

Homo sapiens;

-

pH 7.4, 30°C

0.00109

4-(N-(2-propionylphenyl)sulfamoyl)phenyl pivalate

Homo sapiens;

-

pH 7.4, 30°C

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, 30°C

0.00302

ethyl 2-(4-(pivaloyloxy)benzamido)benzoate

Homo sapiens;

-

pH 7.4, 30°C

0.01

methyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)benzamido)benzoate

Homo sapiens;

-

pH 7.4, 30°C

0.00494

methyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)phenylsulfonamide)benzoate

Homo sapiens;

-

pH 7.4, 30°C

0.00205

methyl 2-(4-(pivaloyloxy)benzamido)benzoate

Homo sapiens;

-

pH 7.4, 30°C

0.01

methyl 2-(4-pivalamidophenylsulfonamido)benzoate

Homo sapiens;

-

pH 7.4, 30°C

0.01

propyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)benzamido)benzoate

Homo sapiens;

-

pH 7.4, 30°C

0.00391

propyl 2-(4-(pivaloyloxy)benzamido)benzoate

Homo sapiens;

-

pH 7.4, 30°C

0.00034

sivelestat

Homo sapiens;

-

pH 7.4, 30°C

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

-

additional information

-

assay methods

7.4

-

assay at

731482, 731997, 732115

8

-

additional information

-

pI: 9.1

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

30

-

assay at

37

-

assay at

6.7

-

calculated from amino acid sequence

7.7

basophilic leukemia cell line

-

calculated from amino acid sequence

9.5

-

-

increased PR-3 on the alveolar macrophage surface in usual interstitial pneumonia relative to healthy controls and sarcoidosis subjects

-

Rattus norvegicus

Q8K597;

-

-

proteinase 3 is considerably more expressed in bone marrow than in the peripheral blood

-

-

inflamed oral epithelial cell

-

-

-

-

-

neutrophilic myelocyte

polymorphonuclear leukocyte

-

717507, 718119

polymorphonuclear neutrophil

-

29719, 29724, 29725, 684453, 687927

-

-

-

additional information

-

-

-

-

-

large amounts

31982

707338

additional information

22000

-

3 * 29000 + 1 * 22000, SDS-PAGE

29000

30000

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

29724

?

4 entries

monomer

-

1 * 29000, SDS-PAGE

652687

multimer

-

3 * 29000 + 1 * 22000, SDS-PAGE

718391

tetramer

-

crystallography

proteolytic modification

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 129–135

-

-

-

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

-

additional information

-

glycosylation at Asn-147, but not at Asn-102, is critical for thermal stability

-70°C

-

-

6 x His-tagged proPR3 purified using affinity chromatography

by anion-exchange chromatography and gel filtration

Candida albicans

-

689931

by nickel-chelating affinity chromatography

-

more than 95% pure

-

-

DELTAAE-PR3(S176A)-His expressed in HEK-293 cells

-

695610

expressed in insect cells

-

expressed in Pichia pastoris

Candida albicans

-

689931

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

-

717575

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

-

718191

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

-

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

-

mast cell lines transfected with PR3

-

mice immunized with recombinant or synthetic human complementary PR3

-

709758

myeloblastin and proteinase 3 are encoded by a single mRNA

-

29718

overexpression of active PR3 and its inactive mutant in HEK-293T cells

-

687618

RBL-2H3 rat mast-cell line stably transfected with PR3 or its inactive mutant S203A

-

685785

recombinant PR3 expressed in HMC1 cells

-

recombinant PR3 expressed in RBL cells

Rattus norvegicus

-

recombinant PR3 wild-type and recombinant PR3 glycosylation variants expressed in HMC-1 cells

-

recombinant PRTN3 protein with an amino-terminal histidine tag produced in SF-9 insect cells by use of a baculovirus expression system

-

710661

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

-

709030

expression of membrane PR3 and CD177 on the same subset of neutrophils

-

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

-

717507

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

-

707316

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

-

707338

F180A/F181A

-

mutant is still able to display membrane PR3 after degranulation, with similar fluorescence intensity as wild-type

F180A/F181A/L228A/F229A

-

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

-

mutant is still able to display membrane PR3 after degranulation, with similar fluorescence intensity as wild-type

L228A

-

mutant is still able to display membrane PR3 after degranulation, with similar fluorescence intensity as wild-type

L228A/F229A

-

mutant is still able to display membrane PR3 after degranulation, with similar fluorescence intensity as wild-type

N102Q

-

glycosylation deficient recombinant PR3 mutant, hydrolytic activity like recombinant PR3-wild-type. N-terminal processing is delayed

N102Q/N147Q

-

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

-

glycosylation deficient recombinant PR3 mutant, is processed like recombinant PR3-wild-type

R193A/R194A/K195A

-

mutant does not affect membrane expression

R193A/R194A/K195A/R227A

-

contrary to wild-type, membrane anchorage is abrogated in mutant

R194A/K195A/R227A

-

mutant does not affect membrane expression

S176A

-

substitution of the active centre

695610

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

S203A

V35M/S38AN/I38BP/Q74R/N113K/N159K/119-122QVAS

-

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

-

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

S203A

Rattus norvegicus

Q8K597;

inactive

665920

additional information

-

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

analysis

-

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

709688

diagnostics

-

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

7 entries

medicine

19 entries

additional information

-

design of potent and highly specific substrates of proteinase 3 and other proteinases optimized in the prime site region