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 language | English |
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Pages (from-to) | 1547-1550 |
Number of pages | 4 |
Journal | Bioorganic & Medicinal Chemistry Letters |
Volume | 12 |
Issue number | 12 |
Publication status | Published - 17 Jun 2002 |