Chloride Supports O2 Activation in the D201G Facial Triad Variant of Factor-Inhibiting Hypoxia Inducible Factor, an α-Ketoglutarate Dependent Oxygenase.
Inorg Chem
; 57(20): 12588-12595, 2018 Oct 15.
Article
in En
| MEDLINE
| ID: mdl-30252455
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 Asp201âGly 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 Asp201âGly FIH variant using X-ray absorption spectroscopy (XAS), which provides insight into the structure of the His2Cl facial triad found in halogenases. The Asp201âGly variant supports anion dependent peptide hydroxylation, demonstrating the requirement for a complete His2X facial triad to support O2 reactivity. Our results indicated that exogenous ligand binding to form a complete His2X facial triad was essential for O2 activation and provides a structural model for the His2Cl-bound nonheme Fe found in halogenases.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oxygen
/
Repressor Proteins
/
Chlorides
/
Mixed Function Oxygenases
/
Iron
Type of study:
Prognostic_studies
Language:
En
Journal:
Inorg Chem
Year:
2018
Document type:
Article
Affiliation country:
United States