Author/Authors :
Luke A. McNeill، نويسنده , , Kirsty S. Hewitson، نويسنده , , Jonathan M. Gleadle، نويسنده , , Louise E. Horsfall، نويسنده , , Neil J. Oldham، نويسنده , , Patrick H. Maxwell، نويسنده , , Christopher W. Pugh، نويسنده , , Peter J. Ratcliffe، نويسنده , , Andrea G. Prescott and Christopher J. Schofield، نويسنده ,
Abstract :
The hypoxic response in animals is mediated by hydroxylation of proline residues in the α-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.
