The use of dioxygen by HIF prolyl hydroxylase (PHD1)

被引：101

作者：

McNeill, LA

Hewitson, KS

Gleadle, JM

Horsfall, LE

Oldham, NJ

Maxwell, PH

Pugh, CW

Ratcliffe, PJ

Schofield, CJ

机构：

[1] Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England

[2] Oxford Ctr Mol Sci, Dyson Perrins Lab, Oxford OX1 3QY, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 12期

基金：

英国工程与自然科学研究理事会; 英国惠康基金; 英国生物技术与生命科学研究理事会;

关键词：

D O I：

10.1016/S0960-894X(02)00219-6

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

收藏

页码：1547 / 1550

页数：4

相关论文

共 28 条

[1]

ARAVIND L, 2001, GENOME BIOL

[2] INCORPORATION OF O-18-LABELED WATER INTO OXYGENATED PRODUCTS PRODUCED BY THE ENZYME DEACETOXY DEACETYLCEPHALOSPORIN C-SYNTHASE [J].

BALDWIN, JE ;

ADLINGTON, RM ;

CROUCH, NP ;

PEREIRA, IAC .

TETRAHEDRON, 1993, 49 (34) :7499-7518

[3] A conserved family of prolyl-4-hydroxylases that modify HIF [J].

Bruick, RK ;

McKnight, SL .

SCIENCE, 2001, 294 (5545) :1337-1340

[4] Structure of proline 3-hydroxylase - Evolution of the family of 2-oxoglutarate dependent oxygenases [J].

Clifton, IJ ;

Hsueh, LC ;

Baldwin, JE ;

Harlos, K ;

Schofield, CJ .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 2001, 268 (24) :6625-6636

[5] Mutagenesis studies on the iron binding ligands of clavaminic acid synthase [J].

Doan, LX ;

Hassan, A ;

Lipscomb, SJ ;

Dhanda, A ;

Zhang, ZH ;

Schofield, CJ .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 279 (01) :240-244

[6] C-elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation [J].

Epstein, ACR ;

Gleadle, JM ;

McNeill, LA ;

Hewitson, KS ;

O'Rourke, J ;

Mole, DR ;

Mukherji, M ;

Metzen, E ;

Wilson, MI ;

Dhanda, A ;

Tian, YM ;

Masson, N ;

Hamilton, DL ;

Jaakkola, P ;

Barstead, R ;

Hodgkin, J ;

Maxwell, PH ;

Pugh, CW ;

Schofield, CJ ;

Ratcliffe, PJ .

CELL, 2001, 107 (01) :43-54

[7] The PAS superfamily: Sensors of environmental and developmental signals [J].

Gu, YZ ;

Hogenesch, JB ;

Bradfield, CA .

ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 2000, 40 :519-561

[8] HIFα targeted for VHL-mediated destruction by proline hydroxylation:: Implications for O2 sensing [J].

Ivan, M ;

Kondo, K ;

Yang, HF ;

Kim, W ;

Valiando, J ;

Ohh, M ;

Salic, A ;

Asara, JM ;

Lane, WS ;

Kaelin, WG .

SCIENCE, 2001, 292 (5516) :464-468

[9] Targeting of HIF-α to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation [J].

Jaakkola, P ;

Mole, DR ;

Tian, YM ;

Wilson, MI ;

Gielbert, J ;

Gaskell, SJ ;

von Kriegsheim, A ;

Hebestreit, HF ;

Mukherji, M ;

Schofield, CJ ;

Maxwell, PH ;

Pugh, CW ;

Ratcliffe, PJ .

SCIENCE, 2001, 292 (5516) :468-472

[10]

Jiang H, 2001, DEV BIOL, V235, P260