Auto-hydroxylation of FIH-1: an Fe(ii), α-ketoglutarate-dependent human hypoxia sensor

• DOI: 10.1039/b809099h
• Publication Date: 2008-08-11T12:02:17Z
• Authors: Yuan-Han Chen; Lindsay M. Comeaux; Stephen J. Eyles; Michael J. Knapp
• Keywords: Hydroxylation; Hypoxia; Chromophore; Hypoxia-Inducible Factors; Reactivity; Hypoxia-Inducible Factor 1

HIF-asparaginyl hydroxylase (FIH-1) normally couples O2-activation to hydroxylation of Asn803 on the α-subunit hypoxia-inducible factor (HIFα), a key step in pO2 sensing; absence HIFα, becomes uncoupled, leading self-hydroxylation at Trp296 and purple Fe(III)–O–Trp chromophore—this alternative reactivity may affect human hypoxia sensing.