title: The use of dioxygen by HIF prolyl hydroxylase (PHD1).
abstract: 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.
authors.affiliation: Oxford Centre for Molecular Sciences, Dyson Perrins Laboratory, South Parks Road, Oxford OX1 3QY, UK.
authors.forename: Luke A
authors.initials: LA
authors.lastname: McNeill
authors.forename: Kirsty S
authors.initials: KS
authors.lastname: Hewitson
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Gleadle
authors.forename: Louise E
authors.initials: LE
authors.lastname: Horsfall
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Oldham
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Maxwell
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Pugh
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Ratcliffe
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Schofield
mesh_terms: 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
chemical_list: D011393:Procollagen-Proline Dioxygenase; D010100:Oxygen