The use of dioxygen by HIF prolyl hydroxylase (PHD1)

  • Bioorg Med Chem Lett. 2002 Jun 17;12(12):1547-50. doi: 10.1016/s0960-894x(02)00219-6.
Luke A McNeill  1 ,  Kirsty S Hewitson ,  Jonathan M Gleadle ,  Louise E Horsfall ,  Neil J Oldham ,  Patrick H Maxwell ,  Christopher W Pugh ,  Peter J Ratcliffe ,  Christopher J Schofield
Affiliations
  • 1. Oxford Centre for Molecular Sciences, Dyson Perrins Laboratory, South Parks Road, Oxford OX1 3QY, UK.
PMID: 12039559 DOI: 10.1016/s0960-894x(02)00219-6
Abstract

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.