The use of dioxygen by HIF prolyl hydroxylase (PHD1).
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.
McNeill
Luke A
LA
Oxford Centre for Molecular Sciences, Dyson Perrins Laboratory, South Parks Road, Oxford OX1 3QY, UK.
Hewitson
Kirsty S
KS
Gleadle
Jonathan M
JM
Horsfall
Louise E
LE
Oldham
Neil J
NJ
Maxwell
Patrick H
PH
Pugh
Christopher W
CW
Ratcliffe
Peter J
PJ
Schofield
Christopher J
CJ
D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006900:Hydroxylation; D008969:Molecular Sequence Data; D010100:Oxygen / Q000378:metabolism*; D011393:Procollagen-Proline Dioxygenase / Q000737:chemistry / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D011393:Procollagen-Proline Dioxygenase; D010100:Oxygen