4D1Z

CDK2 in complex with a Luciferin derivate

Summary for 4D1Z

• Entry DOI: 10.2210/pdb4d1z/pdb
• Related: 4D1X
• Descriptor: CYCLIN-DEPENDENT KINASE 2, (4S)-2-(8-hydroxyquinolin-2-yl)-4,5-dihydro-1,3-thiazole-4-carboxylic acid (3 entities in total)
• Functional Keywords: transferase, cdk2, kinase
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 34525.08

Authors

Rothweiler, U.,Engh, R.A. (deposition date: 2014-05-05, release date: 2015-03-18, Last modification date: 2023-12-20)

Primary citation

Rothweiler, U.,Eriksson, J.,Stensen, W.,Leeson, F.,Engh, R.A.,Svendsen, J.S.
Luciferin and Derivatives as a Dyrk Selective Scaffold for the Design of Protein Kinase Inhibitors.
Eur.J.Med.Chem., 94:140-, 2015

PubMed Abstract: D-Luciferin is widely used as a substrate in luciferase catalysed bioluminescence assays for in vitro studies. However, little is known about cross reactivity and potential interference of D-luciferin with other enzymes. We serendipitously found that firefly luciferin inhibited the CDK2/Cyclin A protein kinase. Inhibition profiling of D-luciferin over a 103-protein kinase panel showed significant inhibition of a small set of protein kinases, in particular the DYRK-family, but also other members of the CMGC-group, including ERK8 and CK2. Inhibition profiling on a 16-member focused library derived from D-luciferin confirms that D-luciferin represents a DYRK-selective chemotype of fragment-like molecular weight. Thus, observation of its inhibitory activity and the initial SAR information reported here promise to be useful for further design of protein kinase inhibitors with related scaffolds.

PubMed: 25768698
DOI: 10.1016/J.EJMECH.2015.02.035

Experimental method

X-RAY DIFFRACTION (1.851 Å)