Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 1 of 1
Full-Text Articles in Inorganic Chemistry
Inhibition And Cofactor Targeting Of Hypoxia-Sensing Proteins, Cornelius Y. Taabazuing
Inhibition And Cofactor Targeting Of Hypoxia-Sensing Proteins, Cornelius Y. Taabazuing
Doctoral Dissertations
Hypoxia Inducible Factor (HIF) is a transcription activator considered to be the main regulator of O2 homeostasis in humans. The transcriptional ability of HIF is regulated by the Fe2+/αKG-dependent enzyme, Factor Inhibiting HIF (FIH). FIH uses molecular oxygen to catalyze hydroxylation of an asparagine residue (Asn803) in the C-terminal transactivation domain (CTAD) of the HIFα subunit, abrogating HIF target gene expression. The mechanism of FIH and other αKG-dependent oxygenases involves the ordered sequential binding of αKG, substrate, and O2, which becomes activated to form a reactive ferryl intermediate that hydroxylates the substrate. The …