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Literature summary for 1.6.3.1 extracted from
- Towards specific NADPH oxidase inhibition by small synthetic peptides (2012), Cell. Mol. Life Sci., 69, 2307-2314.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| A23127 | a calcium ionophore | Homo sapiens | |
| formyl-Met-Leu-Phe | - |
Homo sapiens |  |
| ionomycin | - |
Homo sapiens | |
| additional information | activation of NADPH oxidase in phagocytes can be induced by a large number of inflammatory stimuli such as opsonized bacteria, opsonized zymosan, bacterial formylated peptides such as formyl-Met-Leu-Phe, C5a and platelet-activating factor, and also by pharmacological agents such as calcium ionophores A23127, ionomycin and PKC activators such as phorbol myristate acetate. In intact cells, NADPH oxidase activation is accompanied by phosphorylation of enzyme components p47phox, p67phox, p40phox, p22phox and gp91phox, along with several protein-protein interactions. In human neutrophils, various protein kinases have been implicated in the activation of NADPH oxidase, among which the PKC and MAP kinase families appear to play a major role | Homo sapiens | |
| peptide C5a | - |
Homo sapiens | |
| phorbol myristate acetate | - |
Homo sapiens | |
| platelet-activating factor | - |
Homo sapiens | |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| apocynin | 4-hydroxy-3-methoxyacetophenonesubstituted, a natural molecule structurally related to vanillin, acts on p47phox, requires a peroxidase such as MPO | Homo sapiens | |
| ATDITGPIILQTYRA | a peptide inhibitor derived from human p47phox | Homo sapiens | |
| AYRRNSVRFVRFLN | a peptide inhibitor derived from human p47phox | Homo sapiens | |
| CERLVRFWRSQQKVV | a peptide inhibitor derived from human gp91phox/NOX2 | Homo sapiens | |
| CSTRVRRQLDRNLTFHK | a peptide inhibitor derived from human gp91phox/NOX2 | Homo sapiens | |
| diphenylene iodonium | directly inhibits the activity of enzyme component gp91phox/NOX2, the inhibitor targets the FAD binding sequence found in other flavoproteins and is therefore not specific for NOX2 | Homo sapiens | |
| FAVHHDEEDVITG | a peptide inhibitor derived from human gp91phox/NOX2 | Homo sapiens | |
| FIRHIALLGFEKRFV | a peptide inhibitor derived from human p47phox | Homo sapiens | |
| FLRGSSACCSTRVRRQL | a peptide inhibitor derived from human gp91phox/NOX2 | Homo sapiens | |
| IRNAHSIHQRSRKRL | a peptide inhibitor derived from human p47phox | Homo sapiens | |
| ISNSESGPRGVHFIFNKENF | a peptide inhibitor derived from human gp91phox/NOX2 | Homo sapiens | |
| KTIELQMKKKGFKM | a peptide inhibitor derived from human gp91phox/NOX2 | Homo sapiens | |
| LKLKKIYFYWLCRDTHAF | a peptide inhibitor derived from human gp91phox/NOX2 | Homo sapiens | |
| LKSVWYKYCN | a peptide inhibitor derived from human gp91phox/NOX2 | Homo sapiens | |
| LKSVWYKYCNN | a peptide inhibitor derived from human gp91phox/NOX2 | Homo sapiens | |
| PTKISRCPPHLLDFFK | a peptide inhibitor derived from human p47phox | Homo sapiens | |
| QRRRQARPGPQSPG | a peptide inhibitor derived from human p47phox | Homo sapiens | |
| RFVPSQHYVYMFLVK | a peptide inhibitor derived from human p47phox | Homo sapiens | |
| RGVHFIF | a peptide inhibitor derived from human gp91phox/NOX2 | Homo sapiens | |
| RRNSVRFLQQRRRQA | a peptide inhibitor derived from human p47phox | Homo sapiens | |
| RRSSIRNAHSIHQRSRKRLS | a peptide inhibitor derived from human p47phox | Homo sapiens | |
| RSRKRLSQDAYRRNSVRF | a peptide inhibitor derived from human p47phox | Homo sapiens | |
| RSRKRLSQDAYRRNSVRFLQQR | a peptide inhibitor derived from human p47phox | Homo sapiens | |
| SRKRLSQDAYRRNS | a peptide inhibitor derived from human p47phox | Homo sapiens | |
| STRVRRQLDRNLTF | a peptide inhibitor derived from human gp91phox/NOX2 | Homo sapiens | |
| VWYYRVYDIPPKFFYTRKLL | a peptide inhibitor derived from human gp91phox/NOX2 | Homo sapiens | |
| WWFCQMKAKRGWIPA | a peptide inhibitor derived from human p47phox | Homo sapiens | |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cytosol | in resting cells, enzyme complex components p47phox, p67phox, p40phox and Rac1/2 are localized in the cytosol | Homo sapiens | 5829 | - |
| additional information | in resting cells, enzyme complex components p47phox, p67phox, p40phox and Rac1/2 are localized in the cytosol, whereas p22phox and gp91phox are located in the plasma membrane and membranes of specific granules | Homo sapiens | - |
- |
| plasma membrane | in resting cells, enzyme complex components p22phox and gp91phox are located in the plasma membrane and membranes of specific granules | Homo sapiens | 5886 | - |
| secretory granule | in resting cells, enzyme complex components p22phox and gp91phox are located in the plasma membrane and membranes of specific granules | Homo sapiens | 30141 | - |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| NADH + H+ + O2 | Homo sapiens | - |
NAD+ + H2O2 | - |
? | |
| NADPH + H+ + O2 | Homo sapiens | - |
NADP+ + H2O2 | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| phosphoprotein | in intact cells, NADPH oxidase activation is accompanied by phosphorylation of enzyme components p47phox, p67phox, p40phox, p22phox and gp91phox, along with several protein-protein interactions. P47phox is phosphorylated on multiple sites located in its carboxy-terminal portion, including serines 303-379, which play a central role in NADPH oxidase activation and regulation | Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| neutrophil | - |
Homo sapiens | - |
| phagocyte | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| NADH + H+ + O2 | - |
Homo sapiens | NAD+ + H2O2 | - |
? | |
| NADPH + H+ + O2 | - |
Homo sapiens | NADP+ + H2O2 | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| More | active phagocyte NADPH oxidase is a multicomponent enzyme complex composed of six proteins: p22phox (phox: phagocyte oxidase), gp91phox/NOX2, p47phox, p67phox, p40phox and the small G-protein Rac1 or Rac2, enzyme structure, overview | Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| NADH | - |
Homo sapiens | |
| NADPH | - |
Homo sapiens | |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.001 | - |
pH and temperature not specified in the publication | Homo sapiens | FLRGSSACCSTRVRRQL | |
| 0.002 | - |
pH and temperature not specified in the publication | Homo sapiens | CSTRVRRQLDRNLTFHK | |
| 0.004 | - |
pH and temperature not specified in the publication | Homo sapiens | RGVHFIF | |
| 0.004 | - |
pH and temperature not specified in the publication | Homo sapiens | ISNSESGPRGVHFIFNKENF | |
| 0.01 | - |
pH and temperature not specified in the publication | Homo sapiens | LKSVWYKYCN | |
| 0.01 | - |
pH and temperature not specified in the publication | Homo sapiens | FAVHHDEEDVITG | |
| 0.02 | - |
pH and temperature not specified in the publication | Homo sapiens | KTIELQMKKKGFKM | |
| 0.025 | - |
pH and temperature not specified in the publication | Homo sapiens | LKLKKIYFYWLCRDTHAF | |
| 0.03 | - |
pH and temperature not specified in the publication | Homo sapiens | CERLVRFWRSQQKVV | |
| 0.034 | - |
pH and temperature not specified in the publication | Homo sapiens | VWYYRVYDIPPKFFYTRKLL | |
| 0.04 | - |
pH and temperature not specified in the publication | Homo sapiens | STRVRRQLDRNLTF | |
| 0.05 | - |
pH and temperature not specified in the publication | Homo sapiens | LKSVWYKYCNN | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | excessive NADPH oxidase activation and reactive oxygen species overproduction are believed to participate in disorders such as joint, lung, vascular and intestinal inflammation | Homo sapiens |
| additional information | active phagocyte NADPH oxidase is a multicomponent enzyme complex composed of six proteins: p22phox (phox: phagocyte oxidase), gp91phox/NOX2, p47phox, p67phox, p40phox and the small G-protein Rac1 or Rac2 | Homo sapiens |
| physiological function | reactive oxygen species production by the phagocyte NADPH oxidase is essential for host defenses against pathogens. Reactive oxygen species are very reactive with biological molecules such as lipids, proteins and DNA, potentially resulting in cell dysfunction and tissue insult. Enzyme component P47phox is phosphorylated on multiple sites located in its carboxy-terminal portion, including serines 303-379, which play a central role in NADPH oxidase activation and regulation. In human neutrophils, various protein kinases have been implicated in the activation of NADPH oxidase, among which the PKC and MAP kinase families appear to play a major role | Homo sapiens |
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