5J1V

Crystal structure of human CLK1 in complex with pyrido[3,4-g]quinazoline derivative ZW29 (compound 13)

Summary for 5J1V

• Entry DOI: 10.2210/pdb5j1v/pdb
• Descriptor: Dual specificity protein kinase CLK1, pyrido[3,4-g]quinazoline-2,10-diamine, GLYCEROL, ... (4 entities in total)
• Functional Keywords: transferase, serine/threonine-protein kinase, tyrosine-protein kinase, nucleus, inhibitor, structural genomics consortium, sgc
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus: P49759
• Total number of polymer chains: 3
• Total formula weight: 119562.39

Authors

Chaikuad, A.,Esvan, Y.J.,Zeinyeh, W.,Boibessot, T.,Nauton, L.,Thery, V.,Loaec, N.,Meijer, L.,Giraud, F.,Moreau, P.,Anizon, F.,von Delft, F.,Bountra, C.,Arrowsmith, C.H.,Edwards, A.M.,Knapp, S.,Structural Genomics Consortium (SGC) (deposition date: 2016-03-29, release date: 2016-05-04, Last modification date: 2024-01-10)

Primary citation

Esvan, Y.J.,Zeinyeh, W.,Boibessot, T.,Nauton, L.,Thery, V.,Knapp, S.,Chaikuad, A.,Loaec, N.,Meijer, L.,Anizon, F.,Giraud, F.,Moreau, P.
Discovery of pyrido[3,4-g]quinazoline derivatives as CMGC family protein kinase inhibitors: Design, synthesis, inhibitory potency and X-ray co-crystal structure.
Eur.J.Med.Chem., 118:170-177, 2016

PubMed Abstract: The design and synthesis of new pyrido[3,4-g]quinazoline derivatives is described as well as their protein kinase inhibitory potencies toward five CMGC family members (CDK5, CK1, GSK3, CLK1 and DYRK1A). The interest for this original tricyclic heteroaromatic scaffold as modulators of CLK1/DYRK1A activity was validated by nanomolar potencies (compounds 12 and 13). CLK1 co-crystal structures with two inhibitors revealed the binding mode of these compounds within the ATP-binding pocket.

PubMed: 27128181
DOI: 10.1016/j.ejmech.2016.04.004

Experimental method

X-RAY DIFFRACTION (2.52 Å)