Application | Comment | Organism |
---|---|---|
drug development | the enzyme is a target for design of PHD inhibitors aimed at treating anemia and ischemic disease | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
expression of wild-type and mutant enzymes in Escherichia coli strain BL21(DE3) | Homo sapiens |
Crystallization (Comment) | Organism |
---|---|
recombinant catalytic domain of PHD2 in complex with the C-terminal oxygen-dependent degradation domain of HIF-1alpha, 20°C, 100 nl protein solution containing 40 mg/ml protein in 50 mM Tris-HCl, pH 7.5, 1 mM MnCl2, 1 mM NOG, and 0.1 mM HIF-1alpha CODD556-574 mixed with 100 nl of well solution consisting of 0.2 M MgCl2 and 20% PEG 3350, A tPHD2-Fe2+-B-CODD568-574 crystal is obtained by soaking preformed PHD2181-426-Fe2+-B crystals in 50% sodium malonate, pH 7.5, solution containing 10 mM 4R-hydroxylated Pro564 HIF-1alpha CODD556-574(Hyp564) peptide under anaerobic conditions for 72 h. The PHD2-Fe2+-inhibitor complexes crystallize in an apparently homotrimeric form, method optimization, X-ray diffraction structure determination and analysis at 2.0-2.3 A resolution, molecular replacement | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
additional information | construction of point mutants | Homo sapiens |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Fe2+ | HIF prolyl hydroxylases form unusually stable complexes with their Fe2+ cofactor and 2-oxoglutarate cosubstrate | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
hypoxia-inducible transcription factor + 2-oxoglutarate + O2 | Homo sapiens | i.e. HIF, oxygen-dependent hydroxylation of proline residues in the alpha subunit of hypoxia-inducible transcription factor is central to the hypoxic response in animals. Prolyl hydroxylation of HIFalpha increases its binding to the von Hippel-Lindau protein, thus signaling for degradation via the ubiquitin-proteasome system | hypoxia-inducible transcription factor trans-4-hydroxy-L-proline + succinate + CO2 | - |
? | |
additional information | Homo sapiens | HIF prolyl hydroxylases are related to the collagen prolyl hydroxylases, but form unusually stable complexes with their Fe2+ cofactor and 2-oxoglutarate cosubstrate | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
sveral isozymes | - |
Purification (Comment) | Organism |
---|---|
recombinant wild-type and mutant enzymes from Escherichia coli strain Bl21(DE3) | Homo sapiens |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
procollagen L-proline + 2-oxoglutarate + O2 = procollagen trans-4-hydroxy-L-proline + succinate + CO2 | active site structure and action mode, overview | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
hypoxia-inducible transcription factor + 2-oxoglutarate + O2 | i.e. HIF, oxygen-dependent hydroxylation of proline residues in the alpha subunit of hypoxia-inducible transcription factor is central to the hypoxic response in animals. Prolyl hydroxylation of HIFalpha increases its binding to the von Hippel-Lindau protein, thus signaling for degradation via the ubiquitin-proteasome system | Homo sapiens | hypoxia-inducible transcription factor trans-4-hydroxy-L-proline + succinate + CO2 | - |
? | |
hypoxia-inducible transcription factor + 2-oxoglutarate + O2 | i.e. HIF, the substrate prolyl-residue is bound in a specific conformation and that a significant structural change involving a mobile loop likely occurs concomitant with HIFalpha binding. PHD catalysis involves the mobile region that isolates the hydroxylation site and stabilizes the PHD2-Fe2+-2OG complex. The hydroxylation sites of both NODD and CODD of HIFalpha occur within a conserved LXXLAP motif. In the tPHD2-CODD structure, Leu559CODD, Leu562CODD, and Ala563CODD of the LXXLAP motif form part of the CODD310-helix and make hydrophobic interactions with tPHD2 | Homo sapiens | hypoxia-inducible transcription factor trans-4-hydroxy-L-proline + succinate + CO2 | - |
? | |
additional information | HIF prolyl hydroxylases are related to the collagen prolyl hydroxylases, but form unusually stable complexes with their Fe2+ cofactor and 2-oxoglutarate cosubstrate | Homo sapiens | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
monomer | although the PHD2 protein is monomeric in solution, the PHD2-Fe2+-inhibitor complexes crystallize in an apparently homotrimeric form | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
HIF prolyl hydroxylase | - |
Homo sapiens |
PHD | - |
Homo sapiens |
PHD2 | - |
Homo sapiens |
prolyl hydroxylase domain enzyme | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
physiological function | oxygen-dependent hydroxylation of proline residues in the alpha subunit of hypoxia-inducible transcription factor is central to the hypoxic response in animals. Prolyl hydroxylation of HIFalpha increases its binding to the von Hippel-Lindau protein, thus signaling for degradation via the ubiquitin-proteasome system | Homo sapiens |