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Theses/Dissertations

University of Massachusetts Amherst

2014

Biochemistry, Biophysics, and Structural Biology

Alpha-ketoglutarate dioxygenase

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Full-Text Articles in Life Sciences

Factor Inhibiting Hif's (Fih) Structure Controls O2 Activation And Reactivity, John A. Hangasky Iii Nov 2014

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 ...