6OCC

JAK2 JH2 in complex with JAK190

6OCC の概要

• エントリーDOI: 10.2210/pdb6occ/pdb
• 分子名称: Tyrosine-protein kinase JAK2, GLYCEROL, 2-[4-({5-amino-3-[(4-sulfamoylphenyl)amino]-1H-1,2,4-triazole-1-carbonyl}amino)phenyl]-1,3-oxazole-4-carboxylic acid, ... (4 entities in total)
• 機能のキーワード: pseudokinase domain, inhibitor, complex, transferase, 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: 33697.50

構造登録者

Krimmer, S.G.,Liosi, M.E.,Schlessinger, J.,Jorgensen, W.L. (登録日: 2019-03-22, 公開日: 2020-03-25, 最終更新日: 2023-10-11)

主引用文献

Liosi, M.E.,Krimmer, S.G.,Newton, A.S.,Dawson, T.K.,Puleo, D.E.,Cutrona, K.J.,Suzuki, Y.,Schlessinger, J.,Jorgensen, W.L.
Selective Janus Kinase 2 (JAK2) Pseudokinase Ligands with a Diaminotriazole Core.
J.Med.Chem., 63:5324-5340, 2020

PubMed Abstract: Janus kinases (JAKs) are non-receptor tyrosine kinases that are essential components of the JAK-STAT signaling pathway. Associated aberrant signaling is responsible for many forms of cancer and disorders of the immune system. The present focus is on the discovery of molecules that may regulate the activity of JAK2 by selective binding to the JAK2 pseudokinase domain, JH2. Specifically, the Val617Phe mutation in JH2 stimulates the activity of the adjacent kinase domain (JH1) resulting in myeloproliferative disorders. Starting from a non-selective screening hit, we have achieved the goal of discovering molecules that preferentially bind to the ATP binding site in JH2 instead of JH1. We report the design and synthesis of the compounds and binding results for the JH1, JH2, and JH2 V617F domains, as well as five crystal structures for JH2 complexes. Testing with a selective and non-selective JH2 binder on the autophosphorylation of wild-type and V617F JAK2 is also contrasted.

PubMed: 32329617
DOI: 10.1021/acs.jmedchem.0c00192
主引用文献が同じPDBエントリー

実験手法

X-RAY DIFFRACTION (2.03 Å)