2WAJ

Crystal structure of human Jnk3 complexed with a 1-aryl-3,4- dihydroisoquinoline inhibitor

Summary for 2WAJ

• Entry DOI: 10.2210/pdb2waj/pdb
• Related: 1JNK 1PMN 1PMQ 1PMU 1PMV
• Descriptor: MITOGEN-ACTIVATED PROTEIN KINASE 10, 1-(3-BROMOPHENYL)-7-CHLORO-6-METHOXY-3,4-DIHYDROISOQUINOLINE (3 entities in total)
• Functional Keywords: kinase, epilepsy, transferase, serine/threonine-protein kinase, atp-binding, phosphoprotein, protein kinase, nucleotide-binding
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: P53779
• Total number of polymer chains: 1
• Total formula weight: 42410.31

Authors

Bax, B.D.,Christopher, J.A.,Jones, E.J.,Mosley, J.E. (deposition date: 2009-02-08, release date: 2009-03-31, Last modification date: 2023-12-13)

Primary citation

Christopher, J.A.,Atkinson, F.L.,Bax, B.D.,Brown, M.J.,Champigny, A.C.,Chuang, T.T.,Jones, E.J.,Mosley, J.E.,Musgrave, J.R.
1-Aryl-3,4-Dihydroisoquinoline Inhibitors of Jnk3.
Bioorg.Med.Chem.Lett., 19:2230-, 2009

PubMed Abstract: A series of 1-aryl-3,4-dihydroisoquinoline inhibitors of JNK3 are described. Compounds 20 and 24 are the most potent inhibitors (pIC50 7.3 and 6.9, respectively in a radiometric filter binding assay), with 10- and 1000-fold selectivity over JNK2 and JNK1, respectively, and selectivity within the wider mitogen-activated protein kinase (MAPK) family against p38alpha and ERK2. X-ray crystallography of 16 reveals a highly unusual binding mode where an H-bond acceptor interaction with the hinge region is made by a chloro substituent.

PubMed: 19303774
DOI: 10.1016/J.BMCL.2009.02.098

Experimental method

X-RAY DIFFRACTION (2.4 Å)