The use of dioxygen by HIF prolyl hydroxylase (PHD1).
McNeill LA., Hewitson KS., Gleadle JM., Horsfall LE., Oldham NJ., Maxwell PH., Pugh CW., Ratcliffe PJ., Schofield CJ.
The hypoxic response in animals is mediated by hydroxylation of proline residues in the alpha-subunit of hypoxia inducible factor (HIF). Hydroxylation is catalysed by prolyl-4-hydroxylases (PHD isozymes in humans) which are iron(II) and 2-oxoglutarate dependent oxygenases. Mutation of the arginine proposed to bind 2-oxoglutarate and of the 2His-1-carboxylate iron(II) binding motif in PHD1 dramatically reduces its activity. The source of the oxygen of the product alcohol is (>95%) dioxygen.