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Literature summary for 3.4.21.76 extracted from
- Proteinase 3 phosphonic inhibitors (2019), Biochimie, 166, 142-149 .
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| 7-amino-3-(2-bromoethoxy)-4-chloroisocoumarin | - |
Homo sapiens |  |
| Ac-Pro-Tyr-Asp-AlaP(O-4-ClPh)2 | - |
Homo sapiens | |
| Ac-Pro-Tyr-Phe-AlaP(O-4-ClPh)2 | - |
Homo sapiens | |
| biotin-Pro-Tyr-Asp-AbuP(O-4-ClPh)2 | - |
Homo sapiens | |
| biotin-Pro-Tyr-Asp-AlaP(O-4-ClPh)2 | - |
Homo sapiens | |
| biotin-Pro-Tyr-Asp-NvaP(O-4-ClPh)2 | - |
Homo sapiens | |
| biotin-Val-Pro-LeuP(O-C6H4-4-COOCH3)2 | - |
Homo sapiens | |
| biotin-Val-Pro-LeuP(OPh)2 | - |
Homo sapiens | |
| biotin-Val-Tyr-Asp-AlaP(O-4-ClPh)2 | - |
Homo sapiens | |
| biotin-Val-Tyr-Asp-NvaP(O-4-ClPh)2 | - |
Homo sapiens | |
| biotin-[PEG]66-Pro-Tyr-Asp-AlaP(O-4-ClPh)2 | - |
Homo sapiens | |
| Boc-Val-Pro-ValP(OPh)2 | - |
Homo sapiens | |
| BODIPY-FL-LN-Glu(OBzl)-Lys(Ac)-Pro(4-OBzl)-NvaP(OPh)2 | - |
Homo sapiens | |
| MeO-Suc-Ala-Ala-Pro-ValP(OPh)2 | - |
Homo sapiens | |
| additional information | PR3 inhibitors belong either to the group of peptide analogues (whose structure is directed by the sequence of the substrates) or to non-peptidyl inhibitors, including oxazolidine-2,4-diones, 3,1-benzoxazin-4-ones, isocoumarins, N-hydroxysuccinimides, thiatriazolidines, oximes, Kojic acid derivatives. Analysis of aminophosphonates as potent and selective PR3 inhibitors, overview. Synthesis of alpha-aminoalkylphosphonate diaryl esters. No inhibition by Pro-Tyr-Asp-AlaP(O-C6H4-4-Cl)2 | Homo sapiens | |
| NH2+-Pro-Tyr-Asp-AlaP(O-4-ClPh)2 | - |
Homo sapiens | |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.0011 | - |
2-aminobenzoyl-Val-Ala-Asp-Nva-Ala-Asp-Tyr-Gln-N-(2,4-dinitrophenyl)-ethylenediamine | pH and temperature not specified in the publication | Homo sapiens | |
| 0.0032 | - |
2-aminobenzoyl-Tyr-Tyr-aminobutyl-Asn-Glu-Pro-Tyr(3-NO2)-NH2 | pH and temperature not specified in the publication | Homo sapiens | |
| 0.0033 | - |
2-aminobenzoyl-Val-Ala-Asp-Cys-Arg-Asp-Arg-Gln-N-(2,4-dinitrophenyl)-ethylenediamine | pH and temperature not specified in the publication | Homo sapiens | |
| 0.0123 | - |
2-aminobenzoyl-Val-Ala-Asp-Cys-Ala-Gln-N-(2,4-dinitrophenyl)-ethylenediamine | pH and temperature not specified in the publication | Homo sapiens | |
| 0.0174 | - |
2-aminobenzoyl-Tyr-Tyr-aminobutyl-(5-amino-2-nitrobenzoyl)-Gln-NH2 | pH and temperature not specified in the publication | Homo sapiens | |
| 0.028 | - |
tert-butyloxycarbonyl-Ala-Ala-Val-S-benzyl ester | pH and temperature not specified in the publication | Homo sapiens | |
| 0.0314 | - |
2-aminobenzoyl-Tyr-Tyr-aminobutyl-(5-amino-2-nitrobenzoyl)-NH2 | pH and temperature not specified in the publication | Homo sapiens | |
| 0.05 | - |
O-methyl-succinyl-Ala-Ala-Pro-Ala-S-benzyl ester | pH and temperature not specified in the publication | Homo sapiens | |
| 0.063 | - |
tert-butyloxycarbonyl-Ala-Ala-Nva-S-benzyl ester | pH and temperature not specified in the publication | Homo sapiens | |
| 0.192 | - |
succinyl-Ala-Ala-Nva-S-benzyl ester | pH and temperature not specified in the publication | Homo sapiens | |
| 0.27 | - |
O-methyl-succinyl-Ala-Ala-Pro-Val-4-nitroanilide | pH and temperature not specified in the publication | Homo sapiens | |
| 0.66 | - |
tert-butyloxycarbonyl-Ala-O-4-nitrophenyl ester | pH and temperature not specified in the publication | Homo sapiens | |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| azurophil granule | - |
Homo sapiens | 42582 | - |
| cell membrane | - |
Homo sapiens | - |
- |
| additional information | proteinase 3, also referred to as myeloblastin, is stored not only in azurophilic granules, but also in secretory vesicles and is translocated onto the cell membrane upon stimuli | Homo sapiens | - |
- |
| vesicle | - |
Homo sapiens | 31982 | - |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | Homo sapiens | PR3 is capable of hydrolyzing several extracellular matrix proteins including collagen, elastin, fibronectin and laminin | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | P24158 | - |
- |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 2-aminobenzoyl-Gln-Asp-Met-Ala-Val-Val-Gln-Ser-Val-Pro-Gln-N-(2,4-dinitrophenyl)-ethylenediamine + H2O | - |
Homo sapiens | ? | - |
? | |
| 2-aminobenzoyl-Gln-Pro-Met-Ala-Val-Val-Gln-Ser-Val-Pro-Gln-N-(2,4-dinitrophenyl)-ethylenediamine + H2O | - |
Homo sapiens | ? | - |
? | |
| 2-aminobenzoyl-Tyr-Tyr-aminobutyl-(5-amino-2-nitrobenzoyl)-Gln-NH2 + H2O | - |
Homo sapiens | ? | - |
? | |
| 2-aminobenzoyl-Tyr-Tyr-aminobutyl-(5-amino-2-nitrobenzoyl)-NH2 + H2O | - |
Homo sapiens | ? | - |
? | |
| 2-aminobenzoyl-Tyr-Tyr-aminobutyl-Asn-Glu-Pro-Tyr(3-NO2)-NH2 + H2O | - |
Homo sapiens | ? | - |
? | |
| 2-aminobenzoyl-Val-Ala-Asp-Cys-Ala-Gln-N-(2,4-dinitrophenyl)-ethylenediamine + H2O | - |
Homo sapiens | ? | - |
? | |
| 2-aminobenzoyl-Val-Ala-Asp-Cys-Arg-Asp-Arg-Gln-N-(2,4-dinitrophenyl)-ethylenediamine + H2O | - |
Homo sapiens | ? | - |
? | |
| 2-aminobenzoyl-Val-Ala-Asp-Nva-Ala-Asp-Tyr-Gln-N-(2,4-dinitrophenyl)-ethylenediamine + H2O | - |
Homo sapiens | ? | - |
? | |
| acetyl-Glu(O-benzyl)-Lys(Ac)-Pro(4-O-benzyl)-Nva-7-amido-4-carbamoylmethylcoumarin + H2O | - |
Homo sapiens | ? | - |
? | |
| biotinyl-Val-Tyr-Asp-Nva-4-nitroanilide + H2O | - |
Homo sapiens | ? | - |
? | |
| additional information | PR3 is capable of hydrolyzing several extracellular matrix proteins including collagen, elastin, fibronectin and laminin | Homo sapiens | ? | - |
? | |
| additional information | proteinase 3 can also act via the non-catalytic mechanism. The structure of substrates most susceptible to PR3-mediated hydrolysis provide guidelines for developing ketomethylene compounds, azapeptides, and peptidyl phophonates | Homo sapiens | ? | - |
? | |
| O-methyl-succinyl-Ala-Ala-Pro-Ala-S-benzyl ester + H2O | - |
Homo sapiens | ? | - |
? | |
| O-methyl-succinyl-Ala-Ala-Pro-Val-4-nitroanilide + H2O | - |
Homo sapiens | ? | - |
? | |
| succinyl-Ala-Ala-Nva-S-benzyl ester + H2O | - |
Homo sapiens | ? | - |
? | |
| tert-butyloxycarbonyl-Ala-Ala-Nva-S-benzyl ester + H2O | - |
Homo sapiens | ? | - |
? | |
| tert-butyloxycarbonyl-Ala-Ala-Val-S-benzyl ester + H2O | - |
Homo sapiens | ? | - |
? | |
| tert-butyloxycarbonyl-Ala-O-4-nitrophenyl ester + H2O | - |
Homo sapiens | ? | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| PR3 | - |
Homo sapiens |
| proteinase 3 | - |
Homo sapiens |
General Information
| General Information | Comment | Organism |
|---|---|---|
| metabolism | PR3 concentration in azurophilic granules is approximately 3 times higher than that of human neutrophil elastase and cathepsin G, and the enzyme is less susceptible to inhibition by endogenous serine protease inhibitors correlates with PR3 implication in various pathological processes | Homo sapiens |
| additional information | similarly to azurocidin or CatG, PR3 can also act via the non-catalytic mechanism | Homo sapiens |
| physiological function | the physiological role of PR3 is seen either inside the phagocytic vacuoles or externally where PR3 is engaged in processing of proinflammatory cytokines, receptors, heat shock proteins and other host proteins which after PR3-mediated hydrolysis lead to the generation of antibacterial peptides (e.g. cathelicidin hCAP-18). PR3 is capable of hydrolyzing several extracellular matrix proteins including collagen, elastin, fibronectin and laminin causing the inflammation and tissue injury. PR3 is also known as the antigen in granulomatosis with polyangiitis (GPA), a chronic inflammatory condition that triggers autoimmune response resulting in the production of antineutrophil cytoplasmic antibodies (ANCA). As the binding of ANCA activates neutrophils and therefore increases the level of cell surface PR3, the protein is directly involved in the pathogenesis of the disease | Homo sapiens |
kcat/KM [mM/s]
| kcat/KM Value [1/mMs-1] | kcat/KM Value Maximum [1/mMs-1] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 1.6 | - |
2-aminobenzoyl-Gln-Asp-Met-Ala-Val-Val-Gln-Ser-Val-Pro-Gln-N-(2,4-dinitrophenyl)-ethylenediamine | pH and temperature not specified in the publication | Homo sapiens | |
| 3.05 | - |
O-methyl-succinyl-Ala-Ala-Pro-Val-4-nitroanilide | pH and temperature not specified in the publication | Homo sapiens | |
| 15.15 | - |
tert-butyloxycarbonyl-Ala-O-4-nitrophenyl ester | pH and temperature not specified in the publication | Homo sapiens | |
| 80.51 | - |
biotinyl-Val-Tyr-Asp-Nva-4-nitroanilide | pH and temperature not specified in the publication | Homo sapiens | |
| 95.7 | - |
2-aminobenzoyl-Gln-Pro-Met-Ala-Val-Val-Gln-Ser-Val-Pro-Gln-N-(2,4-dinitrophenyl)-ethylenediamine | pH and temperature not specified in the publication | Homo sapiens | |
| 188.9 | - |
2-aminobenzoyl-Tyr-Tyr-aminobutyl-(5-amino-2-nitrobenzoyl)-NH2 | pH and temperature not specified in the publication | Homo sapiens | |
| 220 | - |
O-methyl-succinyl-Ala-Ala-Pro-Ala-S-benzyl ester | pH and temperature not specified in the publication | Homo sapiens | |
| 274.9 | - |
2-aminobenzoyl-Tyr-Tyr-aminobutyl-(5-amino-2-nitrobenzoyl)-Gln-NH2 | pH and temperature not specified in the publication | Homo sapiens | |
| 292 | - |
2-aminobenzoyl-Val-Ala-Asp-Cys-Ala-Gln-N-(2,4-dinitrophenyl)-ethylenediamine | pH and temperature not specified in the publication | Homo sapiens | |
| 360 | - |
acetyl-Glu(O-benzyl)-Lys(Ac)-Pro(4-O-benzyl)-Nva-7-amido-4-carbamoylmethylcoumarin | pH and temperature not specified in the publication | Homo sapiens | |
| 380 | - |
tert-butyloxycarbonyl-Ala-Ala-Val-S-benzyl ester | pH and temperature not specified in the publication | Homo sapiens | |
| 470 | - |
succinyl-Ala-Ala-Nva-S-benzyl ester | pH and temperature not specified in the publication | Homo sapiens | |
| 1000 | - |
tert-butyloxycarbonyl-Ala-Ala-Nva-S-benzyl ester | pH and temperature not specified in the publication | Homo sapiens | |
| 1596 | - |
2-aminobenzoyl-Tyr-Tyr-aminobutyl-Asn-Glu-Pro-Tyr(3-NO2)-NH2 | pH and temperature not specified in the publication | Homo sapiens | |
| 6500 | - |
2-aminobenzoyl-Val-Ala-Asp-Cys-Arg-Asp-Arg-Gln-N-(2,4-dinitrophenyl)-ethylenediamine | pH and temperature not specified in the publication | Homo sapiens | |
| 7200 | - |
2-aminobenzoyl-Val-Ala-Asp-Nva-Ala-Asp-Tyr-Gln-N-(2,4-dinitrophenyl)-ethylenediamine | pH and temperature not specified in the publication | Homo sapiens | |
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