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/prolyl residues for the C(4)-exo/endo prolyl conformations, respectively.
Loenarz
Christoph
C
Chemistry Research Laboratory and the Oxford Centre for Integrative Systems Biology, Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
Mecinović
Jasmin
J
Chowdhury
Rasheduzzaman
R
McNeill
Luke A
LA
Flashman
Emily
E
Schofield
Christopher J
CJ
D015374:Biosensing Techniques; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000737:chemistry* / Q000378:metabolism; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D010100:Oxygen / Q000378:metabolism*; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism*; D011487:Protein Conformation; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013237:Stereoisomerism; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000378:metabolism
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C490190:EGLN1 protein, human; D011393:Procollagen-Proline Dioxygenase; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D010100:Oxygen