Factor inhibiting hypoxia-inducible factor (FIH) and other asparaginyl hydroxylases.
FIH (Factor inhibiting hypoxia-inducible factor), an asparaginyl beta-hydroxylase belonging to the super-family of 2-oxoglutarate and Fe(II)-dependent dioxygenases, catalyses hydroxylation of Asn-803 of hypoxia-inducible factor, a transcription factor that regulates the mammalian hypoxic response. Only one other asparaginyl beta-hydroxylase, which catalyses hydroxylation of both aspartyl and asparaginyl residues in EGF (epidermal growth factor)-like domains, has been characterized. In the light of recent crystal structures of FIH, we compare FIH with the EGFH (EGF beta-hydroxylase) and putative asparagine/asparaginyl hydroxylases. Sequence analyses imply that EGFH does not contain the HXD/E iron-binding motif characteristic of most of the 2-oxoglutarate oxygenases.
Lancaster
D E
DE
Department of Chemistry and the Oxford Centre for Molecular Sciences, Chemistry Research Laboratory, Mansfield Road, Oxford OX1 3TA, UK.
McDonough
M A
MA
Schofield
C J
CJ
D000595:Amino Acid Sequence; D001216:Asparagine / Q000378:metabolism; D001665:Binding Sites; D007501:Iron / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D008969:Molecular Sequence Data; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D012097:Repressor Proteins; D001216:Asparagine; D007501:Iron; D006899:Mixed Function Oxygenases; D011393:Procollagen-Proline Dioxygenase; C030606:proline, 2-oxoglutarate 3-dioxygenase