Evidence for a stereoelectronic effect in human oxygen sensing

Christoph Loenarz; Jasmin Mecinović; Rasheduzzaman Chowdhury; Luke A McNeill; Emily Flashman; Christopher J Schofield

doi:10.1002/anie.200805427

Evidence for a stereoelectronic effect in human oxygen sensing

Angew Chem Int Ed Engl. 2009;48(10):1784-7. doi: 10.1002/anie.200805427.

Authors

Christoph Loenarz¹, Jasmin Mecinović, Rasheduzzaman Chowdhury, Luke A McNeill, Emily Flashman, Christopher J Schofield

Affiliation

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.

PMID: 19180614
DOI: 10.1002/anie.200805427

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 C(4)-exo/endo prolyl conformations, respectively.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biosensing Techniques
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / chemistry*
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
Hypoxia-Inducible Factor-Proline Dioxygenases
Oxygen / metabolism*
Procollagen-Proline Dioxygenase / metabolism*
Protein Conformation
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Stereoisomerism
Von Hippel-Lindau Tumor Suppressor Protein / metabolism

Substances

Hypoxia-Inducible Factor 1, alpha Subunit
EGLN1 protein, human
Procollagen-Proline Dioxygenase
Hypoxia-Inducible Factor-Proline Dioxygenases
Von Hippel-Lindau Tumor Suppressor Protein
Oxygen

Abstract

Publication types

MeSH terms

Substances

Grants and funding