1MZF

Human Factor inhibiting HIF (FIH1) in Complex with 2-oxoglutarate

1MZF の概要

• エントリーDOI: 10.2210/pdb1mzf/pdb
• 関連するPDBエントリー: 1mze
• 分子名称: factor inhibiting HIF1, FE (II) ION, 2-OXOGLUTARIC ACID, ... (4 entities in total)
• 機能のキーワード: beta-jellyroll, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus (Potential): Q9NWT6
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 40658.35

構造登録者

Dann III, C.E.,Bruick, R.K.,Deisenhofer, J. (登録日: 2002-10-07, 公開日: 2002-11-20, 最終更新日: 2024-04-03)

主引用文献

Dann III, C.E.,Bruick, R.K.,Deisenhofer, J.
Structure of Factor-Inhibiting Hypoxia-Inducible Factor 1: An Asparaginyl Hydroxylase Involved in the Hypoxic Response Pathway.
Proc.Natl.Acad.Sci.USA, 99:15351-15356, 2002

PubMed Abstract: Precise regulation of the evolutionarily conserved hypoxia-inducible transcription factor (HIF) ensures proper adaptation to variations in oxygen availability throughout development and into adulthood. Oxygen-dependent regulation of HIF stability and activity are mediated by hydroxylation of conserved proline and asparagine residues, respectively. Because the relevant prolyl and asparginyl hydroxylases use O(2) 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 pertinent asparaginyl hydroxylase involved in hypoxic signaling. Hydroxylation of the C-terminal transactivation domain (CTAD) of HIF by FIH-1 prevents CTAD association with transcriptional coactivators under normoxic conditions. Consistent with other structurally known hydroxylases, FIH-1 is comprised of a beta-strand jellyroll core with both Fe(II) and the cosubstrate 2-oxoglutarate bound in the active site. Details of the molecular contacts at the active site of FIH-1 have been elucidated and provide a platform for future drug design. Furthermore, the structure reveals the presence of a FIH-1 homodimer that forms in solution and is essential for FIH activity.

PubMed: 12432100
DOI: 10.1073/pnas.202614999

実験手法

X-RAY DIFFRACTION (2.4 Å)