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Keywords:

  • conformational analysis;
  • oxygen sensing;
  • post-translational modifications;
  • signal transduction

Abstract

Thumbnail image of graphical abstract

How PHDs achieve specificity: trans-4-prolyl hydroxylation of the transcription factor HIF occurs with stereochemical retention. Substrate-analogue studies show how the von Hippel Lindau tumor suppressor protein (pVHL) and the oxygen-sensing hydroxylases (PHDs) achieve specificity for hydroxyprolyl/prolyl residues for the C4-exo/endo prolyl conformations, respectively.