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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Asparagine / metabolism*
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Carbon / metabolism*
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Catalysis
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / metabolism*
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Hydroxylation
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Hypoxia-Inducible Factor 1
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Models, Molecular
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Molecular Sequence Data
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Nuclear Magnetic Resonance, Biomolecular
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Nuclear Proteins / chemistry
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Nuclear Proteins / metabolism*
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Transcription Factors*
Substances
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DNA-Binding Proteins
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Hypoxia-Inducible Factor 1
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Nuclear Proteins
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Transcription Factors
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Asparagine
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Carbon