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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.

Type

Journal article

Journal

Bioorg Med Chem Lett

Publication Date

17/06/2002

Volume

12

Pages

1547 - 1550

Keywords

Amino Acid Sequence, Chromatography, High Pressure Liquid, Humans, Hydroxylation, Molecular Sequence Data, Oxygen, Procollagen-Proline Dioxygenase, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization