5USY

JAK2 JH1 in complex with JNJ-7706621

5USY の概要

• エントリーDOI: 10.2210/pdb5usy/pdb
• 関連するPDBエントリー: 5USZ 5UT0 5UT1 5UT2 5UT3 5UT4 5UT5 5UT6
• 分子名称: Tyrosine-protein kinase JAK2, 4-({5-amino-1-[(2,6-difluorophenyl)carbonyl]-1H-1,2,4-triazol-3-yl}amino)benzenesulfonamide, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: kinase 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: 2
• 化学式量合計: 76342.11

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: 2024-11-06)

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 (2 Å)