The use of dioxygen by HIF prolyl hydroxylase (PHD1)

L A McNeill, K S Hewitson, J M Gleadle, L E Horsfall, N J Oldham, P H Maxwell, C W Pugh, P J Ratcliffe, C J Schofield

Research output: Contribution to journalArticlepeer-review

Abstract

The hypoxic response in animals is mediated by hydroxylation of proline residues in the a-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 PHD 1 dramatically reduces its activity. The source of the oxygen of the product alcohol is (>95%) dioxygen. (C) 2002 Published by Elsevier Science.

Original languageEnglish
Pages (from-to)1547-1550
Number of pages4
JournalBioorganic & Medicinal Chemistry Letters
Volume12
Issue number12
Publication statusPublished - 17 Jun 2002

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