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PMID: 12215170 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Hypoxia-inducible factor asparaginyl hydroxylase (FIH-1) catalyses hydroxylation at the beta-carbon of asparagine-803.

The Biochemical journal ·Vol. 367 ·No. Pt 3 ·2002-11-01 ·Pages 571-5

McNeill LA, Hewitson KS, Claridge TD, Seibel JF, Horsfall LE, Schofield CJ

Abstract

Asparagine-803 in the C-terminal transactivation domain of human hypoxia-inducible factor (HIF)-1 alpha-subunit is hydroxylated by factor inhibiting HIF-1 (FIH-1) under normoxic conditions causing abrogation of the HIF-1alpha/p300 interaction. NMR and other analyses of a hydroxylated HIF fragment produced in vitro demonstrate that hydroxylation occurs at the beta-carbon of Asn-803 and imply production of the threo -isomer, in contrast with other known aspartic acid/asparagine hydroxylases that produce the erythro -isomer.

MeSH Terms
Amino Acid Sequence Asparagine/metabolism Carbon/metabolism Catalysis DNA-Binding Proteins/chemistry,metabolism Hydroxylation Hypoxia-Inducible Factor 1 Models, Molecular Molecular Sequence Data Nuclear Magnetic Resonance, Biomolecular Nuclear Proteins/chemistry,metabolism Transcription Factors
Chemicals
DNA-Binding Proteins Hypoxia-Inducible Factor 1 Nuclear Proteins Transcription Factors Asparagine Carbon
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
McNeill Luke A
Oxford Centre for Molecular Sciences, Dyson Perrins Laboratory, University of Oxford, South Parks Road, Oxford OX1 3QY, U.K.
Hewitson Kirsty S
Claridge Timothy D
Seibel Jürgen F
Horsfall Louise E
Schofield Christopher J
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/BJ20021162
Published
2002-11-01
Pages
571-5
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1222951
Subset
IM
External Links
PubMed source DOI: 10.1042/BJ20021162 PMC Full Text View journal details
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