2. Academic Validation
  3. The use of dioxygen by HIF prolyl hydroxylase (PHD1)

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

Affiliation

  • 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.

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