Factor-inhibiting hypoxia-inducible factor (FIH) catalyses the post-translational hydroxylation of histidinyl residues within ankyrin repeat domains

被引：67

作者：

Yang, Ming ^{[1
,2
]}

Chowdhury, Rasheduzzaman ^{[1
,2
]}

Ge, Wei ^{[1
,2
]}

Hamed, Refaat B. ^{[1
,2
,3
]}

McDonough, Michael A. ^{[1
,2
]}

Claridge, Timothy D. W. ^{[1
,2
]}

Kessler, Benedikt M.

Cockman, Matthew E. ^{[1
]}

Ratcliffe, Peter J.

Schofield, Christopher J. ^{[1
,2
]}

机构：

[1] Univ Oxford, Chem Res Lab, Oxford OX3 7BN, England

[2] Univ Oxford, Oxford Ctr Integrat Syst Biol, Oxford OX3 7BN, England

[3] Assiut Univ, Dept Pharmacognosy, Assiut, Egypt

来源：

FEBS JOURNAL | 2011年 / 278卷 / 07期

基金：

英国生物技术与生命科学研究理事会; 英国惠康基金;

关键词：

2-oxoglutarate-dependent dioxygenase; ankyrin repeat domain; factor inhibiting HIF; histidinyl hydroxylation; post-translational hydroxylation; ASPARAGINYL HYDROXYLASE; FACTOR HIF; STREPTOMYCES-VERTICILLUS; ARABIDOPSIS-THALIANA; CONTAINING PROTEINS; BETA-HYDROXYLATION; CRYSTALLOGRAPHY; SUBSTRATE; NOTCH; BIOSYNTHESIS;

D O I：

10.1111/j.1742-4658.2011.08022.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Factor-inhibiting hypoxia-inducible factor (FIH) is an Fe(II)/2-oxogluta-rate-dependent dioxygenase that acts as a negative regulator of the hypoxia-inducible factor (HIF) by catalysing beta-hydroxylation of an asparaginyl residue in its C-terminal transcriptional activation domain (CAD). In addition to the hypoxia-inducible factor C-terminal transcriptional activation domain (HIF-CAD). FIH also catalyses asparaginyl hydroxylation of many ankyrin repeat domain-containing proteins, revealing a broad sequence selectivity. However, there are few reports on the selectivity of FIH for the hydroxylation of specific residues. Here, we report that histidinyl residues within the ankrin repeat domain of tankyrase-2 can be hydroxlated by FIH NMR and crystallographic analyses show that the histidinyl hydroxylation occurs at the beta-position. The results further expand the scope of FIH-catalysed hydroxylations.

引用

页码：1086 / 1097

页数：12

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