PHD2 is a 46-kDa enzyme that consists of an N-terminal domain homologous to MYND zinc finger domains, and a C-terminal domain homologous to the 2-oxoglutarate dioxygenases.
The catalytic domain consists of a double-stranded β-helix core that is stabilized by three α-helices packed along the major β-sheet.
The active site, which is contained in the pocket between the β-sheets, chelates iron(II) through histidine and aspartate coordination.
2-oxoglutarate displaces a water molecule to bind iron as well.
The active site is lined by hydrophobic residues, possibly because such residues are less susceptible to potential oxidative damage by reactive species leaking from the iron center.

PHD2 catalyses the hydroxylation of two sites on HIF-α, which are termed the N-terminal oxygen dependent degradation domain (residues 395-413, NODD) and the C-terminal oxygen dependent degradation domain (residues 556-574, CODD).
These two HIF substrates are usually represented by 19 amino acid long peptides in in vitro experiments.
X-ray crystallography and NMR spectroscopy showed that both peptides bind to the same binding site on PHD2, in a cleft on the PHD2 surface.
An induced fit mechanism was indicated from the structure, in which residues 237-254 adopt a closed loop conformation, whilst in the structure without CODD or NODD, the same residues adopted an open finger-like conformation.
Such conformational change was confirmed by NMR spectroscopy, X-ray crystallography and molecular dynamics calculations.
A recent study found a second peptide binding site on PHD2 although peptide binding to this alternative site did not seem to affect the catalytic activity of the enzyme.
Further studies are required to fully understand the biological significance of this second peptide binding site.

The enzyme has a high affinity for iron(II) and 2-oxoglutarate (also known as α-ketoglutarate), and forms a long-lived complex with these factors.
It has been proposed that cosubstrate and iron concentrations poise the HIF hydroxylases to respond to an appropriate "hypoxic window" for a particular cell type or tissue.
Studies have revealed that PHD2 has a KM for dioxygen slightly above its atmospheric concentration, and PHD2 is thought to be the most important sensor of the cell's oxygen status.
PHD2 is a 46-kDa enzyme that consists of an N-terminal domain homologous to MYND zinc finger domains, and a C-terminal domain homologous to the 2-oxoglutarate dioxygenases. The catalytic domain consists of a double-stranded β-helix core that is stabilized by three α-helices packed along the major β-sheet. The active site, which is contained in the pocket between the β-sheets, chelates iron(II) through histidine and aspartate coordination. 2-oxoglutarate displaces a water molecule to bind iron as well. The active site is lined by hydrophobic residues, possibly because such residues are less susceptible to potential oxidative damage by reactive species leaking from the iron center.
PHD2 catalyses the hydroxylation of two sites on HIF-α, which are termed the N-terminal oxygen dependent degradation domain (residues 395-413, NODD) and the C-terminal oxygen dependent degradation domain (residues 556-574, CODD). These two HIF substrates are usually represented by 19 amino acid long peptides in in vitro experiments. X-ray crystallography and NMR spectroscopy showed that both peptides bind to the same binding site on PHD2, in a cleft on the PHD2 surface. An induced fit mechanism was indicated from the structure, in which residues 237-254 adopt a closed loop conformation, whilst in the structure without CODD or NODD, the same residues adopted an open finger-like conformation. Such conformational change was confirmed by NMR spectroscopy, X-ray crystallography and molecular dynamics calculations. A recent study found a second peptide binding site on PHD2 although peptide binding to this alternative site did not seem to affect the catalytic activity of the enzyme. Further studies are required to fully understand the biological significance of this second peptide binding site.
The enzyme has a high affinity for iron(II) and 2-oxoglutarate (also known as α-ketoglutarate), and forms a long-lived complex with these factors. It has been proposed that cosubstrate and iron concentrations poise the HIF hydroxylases to respond to an appropriate "hypoxic window" for a particular cell type or tissue. Studies have revealed that PHD2 has a KM for dioxygen slightly above its atmospheric concentration, and PHD2 is thought to be the most important sensor of the cell's oxygen status.
EGLN1