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Factor-inhibiting hypoxia-inducible factor (FIH) is an Fe(II)/2-oxoglutarate-dependent dioxygenase that acts as a negative regulator of the hypoxia-inducible factor (HIF) by catalysing β-hydroxylation of an asparaginyl residue in its C-terminal transcriptional activation domain (CAD). In addition to the hypoxia-inducible factor C-terminal transcriptional activation domain (HIF-CAD), FIH also catalyses asparaginyl hydroxylation of many ankyrin repeat domain-containing proteins, revealing a broad sequence selectivity. However, there are few reports on the selectivity of FIH for the hydroxylation of specific residues. Here, we report that histidinyl residues within the ankyrin repeat domain of tankyrase-2 can be hydroxylated by FIH. NMR and crystallographic analyses show that the histidinyl hydroxylation occurs at the β-position. The results further expand the scope of FIH-catalysed hydroxylations.

Original publication

DOI

10.1111/j.1742-4658.2011.08022.x

Type

Journal article

Journal

FEBS J

Publication Date

04/2011

Volume

278

Pages

1086 - 1097

Keywords

Amino Acid Sequence, Ankyrin Repeat, HEK293 Cells, Histidine, Humans, Hydroxylation, Mass Spectrometry, Mixed Function Oxygenases, Models, Molecular, Molecular Sequence Data, Protein Processing, Post-Translational, Protein Structure, Tertiary, Repressor Proteins, Sequence Alignment, Tankyrases