Factor inhibiting hypoxia-inducible factor (FIH) and other asparaginyl hydroxylases

Abstract

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.