5A3U

HIF prolyl hydroxylase 2 (PHD2/EGLN1) in complex with 6-(5-oxo-4-(1H- 1,2,3-triazol-1-yl)-2,5-dihydro-1H-pyrazol-1-yl)nicotinic acid

5A3U の概要

• エントリーDOI: 10.2210/pdb5a3u/pdb
• 関連するPDBエントリー: 2G19 2G1M 4BQW 4BQX 4BQY
• 分子名称: EGL NINE HOMOLOG 1, MANGANESE (II) ION, 6-(5-oxo-4-(1H-1,2,3-triazol-1-yl)-2,5-dihydro-1H-pyrazol-1-yl)nicotinic acid (3 entities in total)
• 機能のキーワード: oxidoreductase, non-heme, iron, 2-oxoglutarate, dioxygenase, hypoxia-inducible factor, hif, hif prolyl hydroxylase domain 2, phd2, egln, oxygenase, hypoxia, dna-binding, metal-binding, transcription, helix-loop-helix-beta, 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)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 85272.30

構造登録者

Chowdhury, R.,Gomez-Perez, V.,Schofield, C.J. (登録日: 2015-06-03, 公開日: 2015-06-17, 最終更新日: 2024-01-10)

主引用文献

Chan, M.C.,Atasoylu, O.,Hodson, E.,Tumber, A.,Leung, I.K.H.,Chowdhury, R.,Gomez-Perez, V.,Demetriades, M.,Rydzik, A.M.,Holt-Martyn, J.,Tian, Y.,Bishop, T.,Claridge, T.D.W.,Kawamura, A.,Pugh, C.W.,Ratcliffe, P.J.,Schofield, C.J.
Potent and Selective Triazole-Based Inhibitors of the Hypoxia-Inducible Factor Prolyl-Hydroxylases with Activity in the Murine Brain.
Plos One, 10:32004-, 2015

PubMed Abstract: As part of the cellular adaptation to limiting oxygen availability in animals, the expression of a large set of genes is activated by the upregulation of the hypoxia-inducible transcription factors (HIFs). Therapeutic activation of the natural human hypoxic response can be achieved by the inhibition of the hypoxia sensors for the HIF system, i.e. the HIF prolyl-hydroxylases (PHDs). Here, we report studies on tricyclic triazole-containing compounds as potent and selective PHD inhibitors which compete with the 2-oxoglutarate co-substrate. One compound (IOX4) induces HIFα in cells and in wildtype mice with marked induction in the brain tissue, revealing that it is useful for studies aimed at validating the upregulation of HIF for treatment of cerebral diseases including stroke.

PubMed: 26147748
DOI: 10.1371/JOURNAL.PONE.0132004

実験手法

X-RAY DIFFRACTION (3.3 Å)