Activating Compound | Comment | Organism | Structure |
---|---|---|---|
ascorbate | - |
Homo sapiens |
Application | Comment | Organism |
---|---|---|
drug development | the unique function of PHD2 makes it a prime target for selective inhibition leading to regulatory control of diseases such as cancer and stroke | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
expression of PHD2 catalytic domain residues 177-426, expression of N-terminally GST-tagged PHD2 in Escherichia coli strain BL21(DE3) | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
2,3-dihydroxypyridine | - |
Homo sapiens | |
2-hydroxypyridine 1-oxide | - |
Homo sapiens | |
3-cyano-6-methyl-2(H)-pyridinone | - |
Homo sapiens | |
3-hydroxy-1,2-dimethyl-4(1H)-pyridinone | - |
Homo sapiens | |
3-hydroxy-2-methyl-4-pyrone | - |
Homo sapiens | |
4-methylcatechol | - |
Homo sapiens | |
4-nitrocatechol | - |
Homo sapiens | |
4-tert-butylcatechol | - |
Homo sapiens | |
5-hydroxy-2-hydroxymethyl-4-pyrone | - |
Homo sapiens | |
5-hydroxy-4-oxo-4H-pyran-2-carboxylic acid | - |
Homo sapiens | |
Cu2+ | binding analysis | Homo sapiens | |
additional information | screening of iron chelators pyridines, hydroxypyrones/hydroxypyridinones, and catechols as inhibitors for PHD2, analysis of selectivity of the inhibitors for PHD2 compared to FIH, EC 1.14.11.30. Ligand binding kinetics and structural analysis, overview. Representative inhibitors bind to the metal center in PHD2 as an 2-oxoglutarate mimic | Homo sapiens |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.007 | - |
2-oxoglutarate | pH 7.0, 37°C | Homo sapiens |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Fe2+ | dependent on, non-heme iron | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 | Homo sapiens | PHD2 hydroxylates Pro402 and/or Pro564 of HIF-1alpha | hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2 | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 | PHD2 hydroxylates Pro402 and/or Pro564 of HIF-1alpha | Homo sapiens | hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2 | - |
? | |
hypoxia-inducible factor-L-proline peptide + 2-oxoglutarate + O2 | peptide substrate is a peptide derived from the natural sequence of HIF-1alpha residues 556-574 | Homo sapiens | hypoxia-inducible factor-trans-4-hydroxy-L-proline peptide + succinate + CO2 | hydroxylation at Pro564 | ? |
Synonyms | Comment | Organism |
---|---|---|
factor inhibiting HIF | - |
Homo sapiens |
FIH | - |
Homo sapiens |
HIF-prolyl hydroxylase domain 2 | - |
Homo sapiens |
PHD2 | - |
Homo sapiens |
prolyl hydroxylase-2 | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7 | - |
assay at | Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.003 | - |
pH 7.0, 37°C | Homo sapiens | 2-hydroxypyridine 1-oxide | |
0.004 | - |
pH 7.0, 37°C | Homo sapiens | 4-methylcatechol | |
0.005 | - |
pH 7.0, 37°C | Homo sapiens | 2,3-dihydroxypyridine | |
0.006 | - |
pH 7.0, 37°C | Homo sapiens | 4-nitrocatechol | |
0.03 | - |
pH 7.0, 37°C | Homo sapiens | 4-tert-butylcatechol | |
0.03 | - |
pH 7.0, 37°C | Homo sapiens | 5-hydroxy-4-oxo-4H-pyran-2-carboxylic acid | |
0.04 | - |
pH 7.0, 37°C | Homo sapiens | 3-hydroxy-1,2-dimethyl-4(1H)-pyridinone | |
0.4 | - |
pH 7.0, 37°C | Homo sapiens | 5-hydroxy-2-hydroxymethyl-4-pyrone | |
1 | - |
above, pH 7.0, 37°C | Homo sapiens | 3-cyano-6-methyl-2(H)-pyridinone | |
1 | - |
above, pH 7.0, 37°C | Homo sapiens | 3-hydroxy-2-methyl-4-pyrone |