Communication

Evidence for a Stereoelectronic Effect in Human Oxygen Sensing†

  1. Christoph Loenarz,
  2. Jasmin Mecinović,
  3. Rasheduzzaman Chowdhury,
  4. Luke A. McNeill Dr.,
  5. Emily Flashman Dr.,
  6. Christopher J. Schofield Prof.

Article first published online: 29 JAN 2009

DOI: 10.1002/anie.200805427

Issue

Angewandte Chemie International Edition

Angewandte Chemie International Edition

Volume 48, Issue 10, pages 1784–1787, February 23, 2009

Additional Information

How to Cite

Loenarz, C., Mecinović, J., Chowdhury, R., McNeill, Luke A., Flashman, E. and Schofield, Christopher J. (2009), Evidence for a Stereoelectronic Effect in Human Oxygen Sensing. Angew. Chem. Int. Ed., 48: 1784–1787. doi: 10.1002/anie.200805427

Author Information

  1. Chemistry Research Laboratory and the Oxford Centre for Integrative Systems Biology, Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA (UK), Fax: (+44) 1865-275-674 http://www.chem.ox.ac.uk/oc/cjschofield

  1. †

    Supported by the BBSRC and The Wellcome Trust; Studienstiftung, Dr.-Carl-Duisberg-Stiftung, and Rhodes Trust (C.L.); Newton-Abraham Fund (J.M.); Commonwealth Scholarship Commission (R.C.). We thank J. D. Webb and Prof. Dr. M. E. Maier (University of Tübingen) for assistance with [35S]-pVHL assays and help with synthesis, respectively. Abbreviations: 2OG, 2-oxoglutarate; HIF, hypoxia inducible factor; PHD, prolyl hydroxylase domain; pVHL, von Hippel Lindau protein; ESI, electrospray ionization.

Publication History

  1. Issue published online: 17 FEB 2009
  2. Article first published online: 29 JAN 2009
  3. Manuscript Revised: 3 DEC 2008
  4. Manuscript Received: 6 NOV 2008

Funded by

  • BBSRC
  • The Wellcome Trust
  • Studienstiftung
  • Dr.-Carl-Duisberg-Stiftung
  • Rhodes Trust
  • Newton-Abraham Fund
  • Commonwealth Scholarship Commission

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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.

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