[HTML][HTML] Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1α
JM Elkins, KS Hewitson, LA McNeill, JF Seibel… - Journal of Biological …, 2003 - ASBMB
The activity of the transcription factor hypoxia-inducible factor (HIF) is regulated by oxygen-
dependent hydroxylation. Under normoxic conditions, hydroxylation of proline residues
triggers destruction of its α-subunit while hydroxylation of Asn 803 in the C-terminal
transactivation domain of HIF-1α (CAD) prevents its interaction with p300. Here we report
crystal structures of the asparagine hydroxylase (factor-inhibiting HIF, FIH) complexed with
Fe (II), 2-oxoglutarate cosubstrate, and CAD fragments, which reveal the structural basis of …
dependent hydroxylation. Under normoxic conditions, hydroxylation of proline residues
triggers destruction of its α-subunit while hydroxylation of Asn 803 in the C-terminal
transactivation domain of HIF-1α (CAD) prevents its interaction with p300. Here we report
crystal structures of the asparagine hydroxylase (factor-inhibiting HIF, FIH) complexed with
Fe (II), 2-oxoglutarate cosubstrate, and CAD fragments, which reveal the structural basis of …
