Structural Basis for the Interaction between Casein Kinase 1 Delta and a Potent and Selective Inhibitor

Casein kinase 1 delta (CK1δ) and its closest homologue CK1ε are key regulators of diverse cellular growth and survival processes such as Wnt signaling, DNA repair, and circadian rhythms. We report three crystal structures of the kinase domain of human CK1δ, one apo and two complexed with a potent an...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2012-01, Vol.55 (2), p.956-960
Main Authors: Long, Alexander, Zhao, Huilin, Huang, Xin
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Apoenzymes - antagonists & inhibitors
Apoenzymes - chemistry
Casein Kinase Idelta - antagonists & inhibitors
Casein Kinase Idelta - chemistry
Casein Kinase Iepsilon - antagonists & inhibitors
Casein Kinase Iepsilon - chemistry
Catalytic Domain
Crystallography, X-Ray
Humans
Imidazoles - chemistry
Ligands
Models, Molecular
Molecular Sequence Data
Protein Conformation
Pyrimidines - chemistry
Quantitative Structure-Activity Relationship
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Summary:Casein kinase 1 delta (CK1δ) and its closest homologue CK1ε are key regulators of diverse cellular growth and survival processes such as Wnt signaling, DNA repair, and circadian rhythms. We report three crystal structures of the kinase domain of human CK1δ, one apo and two complexed with a potent and selective CK1δ/ε inhibitor PF670462 in two different crystal forms. These structures provide a molecular basis for the strong and specific inhibitor interactions and suggest clues for further development of CK1δ/ε inhibitors.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm201387s