5UT3

JAK2 JH2 in complex with IKK-2 Inhibitor VI

5UT3 の概要

• エントリーDOI: 10.2210/pdb5ut3/pdb
• 分子名称: Tyrosine-protein kinase JAK2, 5-PHENYL-2-UREIDOTHIOPHENE-3-CARBOXAMIDE, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: pseudokinase domain, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33717.59

構造登録者

Puleo, D.E.,Schlessinger, J. (登録日: 2017-02-14, 公開日: 2017-06-07, 最終更新日: 2023-10-04)

主引用文献

Puleo, D.E.,Kucera, K.,Hammaren, H.M.,Ungureanu, D.,Newton, A.S.,Silvennoinen, O.,Jorgensen, W.L.,Schlessinger, J.
Identification and Characterization of JAK2 Pseudokinase Domain Small Molecule Binders.
ACS Med Chem Lett, 8:618-621, 2017

PubMed Abstract: Janus kinases (JAKs) regulate hematopoiesis via the cytokine-mediated JAK-STAT signaling pathway. JAKs contain tandem C-terminal pseudokinase (JH2) and tyrosine kinase (JH1) domains. The JAK2 pseudokinase domain adopts a protein kinase fold and, despite its pseudokinase designation, binds ATP with micromolar affinity. Recent evidence shows that displacing ATP from the JAK2 JH2 domain alters the hyperactivation state of the oncogenic JAK2 V617F protein while sparing the wild type JAK2 protein. In this study, small molecule binders of JAK2 JH2 were identified via an screen. Top hits were characterized using biophysical and structural approaches. Development of pseudokinase-selective compounds may offer novel pharmacological opportunities for treating cancers driven by JAK2 V617F and other oncogenic JAK mutants.

PubMed: 28626521
DOI: 10.1021/acsmedchemlett.7b00153

実験手法

X-RAY DIFFRACTION (1.501 Å)