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Summary: Structure of factor-inhibiting hypoxia-inducible
factor 1: An asparaginyl hydroxylase involved
in the hypoxic response pathway
Charles E. Dann III*
, Richard K. Bruick
, and Johann Deisenhofer*
*Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard,
Dallas, TX 75390
Contributed by Johann Deisenhofer, October 10, 2002
Precise regulation of the evolutionarily conserved hypoxia-induc-
ible transcription factor (HIF) ensures proper adaptation to varia-
tions in oxygen availability throughout development and into
adulthood. Oxygen-dependent regulation of HIF stability and ac-
tivity are mediated by hydroxylation of conserved proline and
asparagine residues, respectively. Because the relevant prolyl and
asparginyl hydroxylases use O2 to effect these posttranslational
modifications, these enzymes are implicated as direct oxygen
sensors in the mammalian hypoxic response pathway. Here we
present the structure of factor-inhibiting HIF-1 (FIH-1), the perti-
nent asparaginyl hydroxylase involved in hypoxic signaling. Hy-
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