期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 12, 期 12, 页码 1547-1550出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0960-894X(02)00219-6
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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.
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