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

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