5UT2

JAK2 JH2 in complex with PRT062607

Summary for 5UT2

• Entry DOI: 10.2210/pdb5ut2/pdb
• Related: 5USY 5USZ 5UT0 5UT1 5UT3 5UT4 5UT5 5UT6
• Descriptor: Tyrosine-protein kinase JAK2, GLYCEROL, 2-{[(1R,2S)-2-aminocyclohexyl]amino}-4-{[3-(2H-1,2,3-triazol-2-yl)phenyl]amino}pyrimidine-5-carboxamide, ... (5 entities in total)
• Functional Keywords: pseudokinase domain, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 33757.64

Authors

Puleo, D.E.,Schlessinger, J. (deposition date: 2017-02-14, release date: 2017-06-07, Last modification date: 2023-10-04)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.75 Å)