The use of dioxygen by HIF prolyl hydroxylase (PHD1)

L A  McNeill; K S  Hewitson; J M  Gleadle; L E  Horsfall; N J  Oldham; P H  Maxwell; C W  Pugh; P J  Ratcliffe; C J  Schofield

The use of dioxygen by HIF prolyl hydroxylase (PHD1)

L A McNeill, K S Hewitson, J M Gleadle, L E Horsfall, N J Oldham, P H Maxwell, C W Pugh, P J Ratcliffe, C J Schofield

School of Biological Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	1547-1550
Number of pages	4
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	12
Issue number	12
Publication status	Published - 17 Jun 2002

Cite this

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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 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.",

author = "McNeill, {L A} and Hewitson, {K S} and Gleadle, {J M} and Horsfall, {L E} and Oldham, {N J} and Maxwell, {P H} and Pugh, {C W} and Ratcliffe, {P J} and Schofield, {C J}",

year = "2002",

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language = "English",

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journal = "Bioorganic & Medicinal Chemistry Letters",

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T1 - The use of dioxygen by HIF prolyl hydroxylase (PHD1)

AU - McNeill, L A

AU - Hewitson, K S

AU - Gleadle, J M

AU - Horsfall, L E

AU - Oldham, N J

AU - Maxwell, P H

AU - Pugh, C W

AU - Ratcliffe, P J

AU - Schofield, C J

PY - 2002/6/17

Y1 - 2002/6/17

N2 - 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.

AB - 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.

M3 - Article

VL - 12

SP - 1547

EP - 1550

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

SN - 0960-894X

IS - 12

ER -

The use of dioxygen by HIF prolyl hydroxylase (PHD1)

Abstract

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