Hypoxia-inducible factor asparaginyl hydroxylase (FIH-1) catalyses hydroxylation at the beta-carbon of asparagine-803.
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.
McNeill
Luke A
LA
Oxford Centre for Molecular Sciences, Dyson Perrins Laboratory, University of Oxford, South Parks Road, Oxford OX1 3QY, U.K.
Hewitson
Kirsty S
KS
Claridge
Timothy D
TD
Seibel
Jürgen F
JF
Horsfall
Louise E
LE
Schofield
Christopher J
CJ
D000595:Amino Acid Sequence; D001216:Asparagine / Q000378:metabolism*; D002244:Carbon / Q000378:metabolism*; D002384:Catalysis; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006900:Hydroxylation; D051793:Hypoxia-Inducible Factor 1; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D051793:Hypoxia-Inducible Factor 1; D009687:Nuclear Proteins; D014157:Transcription Factors; D001216:Asparagine; D002244:Carbon