4BQY

HIF prolyl hydroxylase 2 (PHD2/ EGLN1) in complex with Fe(II) and N-[(1-chloro-4-hydroxyisoquinolin-3-yl)carbonyl]alanine

4BQY の概要

• エントリーDOI: 10.2210/pdb4bqy/pdb
• 関連するPDBエントリー: 4BQW 4BQX
• 分子名称: EGL NINE HOMOLOG 1, FE (II) ION, (2S)-2-{[(1-chloro-4-hydroxyisoquinolin-3-yl)carbonyl]amino}propanoic acid, ... (4 entities in total)
• 機能のキーワード: oxidoreductase, 2-oxoglutarate, dioxygenase, egln, oxygenase, hypoxia, dna-binding, metal-binding, transcription, dsbh, facial triad, asparaginyl/ aspartyl hydroxylase, transcription and epigenetic regulation, signaling, development, cell structure, ankyrin repeat domain, ard, beta-hydroxylation, transcription activator/inhibitor, phosphorylation, s-nitrosylation
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm : Q9GZT9
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 28447.48

構造登録者

Chowdhury, R.,McDonough, M.A.,Yeoh, K.K.,Schofield, C.J. (登録日: 2013-06-03, 公開日: 2013-06-19, 最終更新日: 2024-10-16)

主引用文献

Chowdhury, R.,Candela-Lena, J.I.,Chan, M.C.,Greenald, D.J.,Yeoh, K.K.,Tian, Y.M.,McDonough, M.A.,Tumber, A.,Rose, N.R.,Conejo-Garcia, A.,Demetriades, M.,Mathavan, S.,Kawamura, A.,Lee, M.K.,van Eeden, F.,Pugh, C.W.,Ratcliffe, P.J.,Schofield, C.J.
Selective small molecule probes for the hypoxia inducible factor (HIF) prolyl hydroxylases.
ACS Chem. Biol., 8:1488-1496, 2013

PubMed Abstract: The hypoxia inducible factor (HIF) system is central to the signaling of low oxygen (hypoxia) in animals. The levels of HIF-α isoforms are regulated in an oxygen-dependent manner by the activity of the HIF prolyl-hydroxylases (PHD or EGLN enzymes), which are Fe(II) and 2-oxoglutarate (2OG) dependent oxygenases. Here, we describe biochemical, crystallographic, cellular profiling, and animal studies on PHD inhibitors including selectivity studies using a representative set of human 2OG oxygenases. We identify suitable probe compounds for use in studies on the functional effects of PHD inhibition in cells and in animals.

PubMed: 23683440
DOI: 10.1021/cb400088q

実験手法

X-RAY DIFFRACTION (1.53 Å)