title: Auto-hydroxylation of FIH-1: an Fe(ii), alpha-ketoglutarate-dependent human hypoxia sensor.
abstract: HIF-asparaginyl hydroxylase (FIH-1) normally couples O(2)-activation to hydroxylation of Asn(803) on the alpha-subunit of the hypoxia-inducible factor (HIFalpha), a key step in pO(2) sensing; in the absence of HIFalpha, O(2)-activation becomes uncoupled, leading to self-hydroxylation at Trp(296) and a purple Fe(iii)-O-Trp chromophore-this alternative reactivity may affect human hypoxia sensing.
authors.affiliation: Department of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003, USA.
authors.forename: Yuan-Han
authors.initials: YH
authors.lastname: Chen
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Comeaux
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Eyles
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Knapp
mesh_terms: D020134:Catalytic Domain; D004566:Electrodes; D005296:Ferrous Compounds / Q000737:chemistry*; D006801:Humans; D006900:Hydroxylation; D000860:Hypoxia; D007656:Ketoglutaric Acids / Q000737:chemistry*; D006899:Mixed Function Oxygenases; D010100:Oxygen / Q000032:analysis*; D012097:Repressor Proteins / Q000737:chemistry*; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D013053:Spectrophotometry
chemical_list: D005296:Ferrous Compounds; D007656:Ketoglutaric Acids; D012097:Repressor Proteins; D006899:Mixed Function Oxygenases; C439790:HIF1AN protein, human; D010100:Oxygen