Structure
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.
The enzyme has a high affinity for iron(II) and 2-oxoglutarate, 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.
Read more about this topic: EGLN1
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