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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Factor Inhibiting Hif's (Fih) Structure Controls O2 Activation And Reactivity, John A. Hangasky Iii
Factor Inhibiting Hif's (Fih) Structure Controls O2 Activation And Reactivity, John A. Hangasky Iii
Doctoral Dissertations
Factor Inhibiting HIF (FIH) is a Fe(II)-αKG dependent oxygenase that acts as a cellular oxygen sensor in humans. FIH regulates the transcriptional activity of the hypoxia-inducible factor-1 (HIF-1a or HIF), a transcription factor responsible cellular O2 homeostasis. Hydroxylation of the target residue HIF-Asn803, found in the C-terminal transactivation domain (CTAD), inactivates HIF-dependent gene expression. Central to FIH’s function is the activation of O2 after CTAD binding. The mechanistic and structural features of FIH leading to tight coupling between CTAD binding and subsequent O2-activation and reactivity are key for efficient O2 sensing. Our mechanistic …