Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 1.14.11.29 extracted from

  • Flagg, S.C.; Martin, C.B.; Taabazuing, C.Y.; Holmes, B.E.; Knapp, M.J.
    Screening chelating inhibitors of HIF-prolyl hydroxylase domain 2 (PHD2) and factor inhibiting HIF (FIH) (2012), J. Inorg. Biochem., 113, 25-30.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
ascorbate
-
Homo sapiens

Application

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(Commentary)

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

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 [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.007
-
2-oxoglutarate pH 7.0, 37°C Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Fe2+ dependent on, non-heme iron Homo sapiens

Natural Substrates/ Products (Substrates)

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

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Substrates and Products (Substrate)

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

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 [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7
-
assay at Homo sapiens

IC50 Value

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