Asparagine beta-hydroxylation stabilizes the ankyrin repeat domain fold

Leanne Kelly, Michael A McDonough, Mathew L Coleman, Peter J Ratcliffe, Christopher J Schofield

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)


Ankyrin repeats (ARs) are one of the most common structural motifs among eukaryotic proteins. Recent analyses have shown that factor inhibiting hypoxia-inducible factor (FIH) catalyses the hydroxylation of highly conserved Asn-residues within ankyrin repeat domains (ARDs). However, the effect of Asn-hydroxylation on ARD structure is unknown. Supporting the proposal that FIH-mediated ARD hydroxylation is ubiquitous we report that consensus ARD proteins are FIH substrates both in vitro and in vivo. X-ray diffraction analyses revealed that hydroxylation does not alter the archetypical ARD conformation in the crystalline state. However, other biophysical analyses revealed that hydroxylation significantly stabilizes the ARD fold in solution. We propose that intracellular protein hydroxylation is much more common than previously thought and that one of its roles is stabilization of localized regions of ARD folds.
Original languageEnglish
Pages (from-to)52-8
Number of pages7
JournalMolecular BioSystems
Issue number1
Publication statusPublished - Jan 2009


  • Ankyrin Repeat
  • Asparagine
  • Cell Line
  • Crystallography, X-Ray
  • Humans
  • Hydroxylation
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Folding
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Substrate Specificity


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