Chloride Supports O₂ Activation in the D201G Facial Triad Variant of Factor-Inhibiting Hypoxia Inducible Factor, an α-Ketoglutarate Dependent Oxygenase.

ABSTRACT: α-Ketoglutarate (αKG) dependent oxygenases comprise a large superfamily of enzymes that activate O₂ for varied reactions. While most of these enzymes contain a nonheme Fe bound by a His₂(Asp/Glu) facial triad, a small number of αKG-dependent halogenases require only the two His ligands to bind Fe and activate O₂. The enzyme "factor inhibiting HIF" (FIH) contains a His₂Asp facial triad and selectively hydroxylates polypeptides; however, removal of the Asp ligand in the Asp201→Gly variant leads to a highly active enzyme, seemingly without a complete facial triad. Herein, we report on the formation of an Fe-Cl cofactor structure for the Asp201→Gly FIH variant using X-ray absorption spectroscopy (XAS), which provides insight into the structure of the

SUBMITTER: Chaplin VD 

PROVIDER: S-EPMC6496954 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature