Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

The hypoxic response in animals is mediated via the transcription factor hypoxia-inducible factor (HIF). An oxygen-sensing component of the HIF system is provided by Fe(II) and 2-oxoglutarate-dependent oxygenases that catalyse the posttranslational hydroxylation of the HIF-α subunit. It is proposed that the activity of the HIF hydroxylases can be regulated by their reaction with nitric oxide. We describe biochemical and biophysical studies on the reaction of prolyl hydroxylase domain-containing enzyme (PHD) isoform 2 (EGLN1) with nitric oxide and a nitric oxide transfer reagent. The combined results reveal the potential for the catalytic domain of PHD2 to react with nitric oxide both at its Fe(II) and at cysteine residues. Although the biological significance is unclear, the results suggest that the reaction of PHD2 with nitric oxide has the potential to be complex and are consistent with proposals based on cellular studies that nitric oxide may regulate the hypoxic response by direct reaction with the HIF hydroxylases.

Original publication

DOI

10.1016/j.jmb.2011.04.075

Type

Journal article

Journal

J Mol Biol

Publication Date

08/07/2011

Volume

410

Pages

268 - 279

Keywords

Amino Acid Sequence, Crystallography, X-Ray, Humans, Hypoxia, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor-Proline Dioxygenases, Molecular Sequence Data, Nitric Oxide, Procollagen-Proline Dioxygenase, Protein Structure, Tertiary, Spectrometry, Mass, Electrospray Ionization, Tandem Mass Spectrometry