Evidence for a Stereoelectronic Effect in Human Oxygen Sensing

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/...

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Veröffentlicht in:	Angewandte Chemie (International ed.) 2009-01, Vol.48 (10), p.1784-1787
Hauptverfasser:	Loenarz, Christoph, Mecinović, Jasmin, Chowdhury, Rasheduzzaman, McNeill, Luke A, Flashman, Emily, Schofield, Christopher J
Format:	Artikel
Sprache:	eng
Schlagworte:	Biosensing Techniques conformational analysis Humans Hypoxia-Inducible Factor 1, alpha Subunit - chemistry Hypoxia-Inducible Factor 1, alpha Subunit - metabolism Hypoxia-Inducible Factor-Proline Dioxygenases Oxygen - metabolism oxygen sensing post‐translational modifications Procollagen-Proline Dioxygenase - metabolism Protein Conformation signal transduction Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Stereoisomerism Von Hippel-Lindau Tumor Suppressor Protein - metabolism
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Zusammenfassung:	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.
ISSN:	1433-7851 1521-3773
DOI:	10.1002/anie.200805427