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Cover Picture: ESI‐MS Studies on Prolyl Hydroxylase Domain 2 Reveal a New Metal Binding Site (ChemMedChem 4/2008)
Author(s) -
Mecinović Jasmin,
Chowdhury Rasheduzzaman,
Liénard Benoît M. R.,
Flashman Emily,
Buck Matthew R. G.,
Oldham Neil J.,
Schofield Christopher J.
Publication year - 2008
Publication title -
chemmedchem
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200890014
Subject(s) - hydroxylation , chemistry , protein subunit , transcription factor , stereochemistry , electrospray ionization , enzyme , hypoxia inducible factors , mass spectrometry , biochemistry , gene , chromatography
The cover picture shows a view from a crystal structure of prolyl hydroxylase domain 2 (PHD2), which is the major PHD that catalyses HIF‐α hydroxylation under normoxic conditions. The hypoxic response in animals is mediated by the transcription factor hypoxia inducible factor (HIF). Levels of the HIF‐α subunit are regulated by PHD‐catalysed prolyl hydroxylation, which signals for the degradation of HIF‐α under normoxic conditions. The requirement of the PHDs for molecular oxygen enables them to act as oxygen sensors. Inhibition of the PHDs in order to activate the hypoxic response is of interest for therapeutic benefit. Alongside the PHD2 structure are shown electrospray ionisation mass spectrometric data, described in the Communication by C. J. Schofield et al. on p. 569 ff., that reveal a second metal binding site on the enzyme.