3HQU

PHD2:Fe:UN9:partial HIF1-alpha substrate complex

3HQU の概要

• エントリーDOI: 10.2210/pdb3hqu/pdb
• 関連するPDBエントリー: 2G1M 3HQR
• 分子名称: Egl nine homolog 1, Hypoxia-inducible factor 1 alpha, FE (II) ION, ... (5 entities in total)
• 機能のキーワード: double stranded beta-helix, alternative splicing, congenital erythrocytosis, dioxygenase, disease mutation, iron, metal-binding, oxidoreductase, vitamin c, zinc, zinc-finger, activator, cytoplasm, dna-binding, hydroxylation, isopeptide bond, nucleus, phosphoprotein, polymorphism, s-nitrosylation, transcription, transcription regulation, ubl conjugation, oxidoreductase-transcription complex, oxidoreductase/transcription
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm : Q9GZT9 Q16665
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 29888.11

構造登録者

Chowdhury, R.,McDonough, M.A.,Schofield, C.J. (登録日: 2009-06-08, 公開日: 2009-07-28, 最終更新日: 2023-11-01)

主引用文献

Chowdhury, R.,McDonough, M.A.,Mecinovic, J.,Loenarz, C.,Flashman, E.,Hewitson, K.S.,Domene, C.,Schofield, C.J.
Structural basis for binding of hypoxia-inducible factor to the oxygen-sensing prolyl hydroxylases
Structure, 17:981-989, 2009

PubMed Abstract: The oxygen-dependent hydroxylation of proline residues in the alpha subunit of hypoxia-inducible transcription factor (HIFalpha) is central to the hypoxic response in animals. Prolyl hydroxylation of HIFalpha increases its binding to the von Hippel-Lindau protein (pVHL), so signaling for degradation via the ubiquitin-proteasome system. The HIF prolyl hydroxylases (PHDs, prolyl hydroxylase domain enzymes) are related to the collagen prolyl hydroxylases, but form unusually stable complexes with their Fe(II) cofactor and 2-oxoglutarate cosubstrate. We report crystal structures of the catalytic domain of PHD2, the most important of the human PHDs, in complex with the C-terminal oxygen-dependent degradation domain of HIF-1alpha. Together with biochemical analyses, the results reveal that PHD catalysis involves a mobile region that isolates the hydroxylation site and stabilizes the PHD2.Fe(II).2OG complex. The results will be of use in the design of PHD inhibitors aimed at treating anemia and ischemic disease.

PubMed: 19604478
DOI: 10.1016/j.str.2009.06.002

実験手法

X-RAY DIFFRACTION (2.3 Å)