Factor-inhibiting hypoxia-inducible factor (FIH) catalyses the post-translational hydroxylation of histidinyl residues within ankyrin repeat domains.
Bottom Line: However, there are few reports on the selectivity of FIH for the hydroxylation of specific residues.NMR and crystallographic analyses show that the histidinyl hydroxylation occurs at the β-position.The results further expand the scope of FIH-catalysed hydroxylations.
Affiliation: Oxford Centre for Integrative Systems Biology, University of Oxford, Oxford, UK.Show MeSH
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Mentions: To investigate whether FIH-catalysed His hydroxylation can occur in other AR sequences, we searched for naturally occurring AR sequences containing an ‘LxxxxxDVH’ motif with the His residue located at the conserved hydroxylation position, and tested the corresponding peptides as FIH substrates (Fig. 6). In addition to tankyrase-2, peptides derived from tankyrase-1, GA-binding protein subunit beta-2 (GABPB2) and the transient receptor potential vanilloid-4 (TRPV4) ARD all displayed +16 Da mass shifts after reaction with FIH (Fig. 6B). MS/MS analyses assigned sites of hydroxylation to His 711 in the tankyrase-1 sequence (Fig. S3) and His 265 in the TRPV4 sequence (Fig. S4), both of which are located within the β-hairpin loop at the structurally conserved hydroxylation position.
Affiliation: Oxford Centre for Integrative Systems Biology, University of Oxford, Oxford, UK.