Abstract
Casein kinase 1 epsilon (CK1ε) and its closest homologue CK1δ are key regulators of diverse cellular processes. We report two crystal structures of PF4800567, a potent and selective inhibitor of CK1ε, bound to the kinase domains of human CK1ε and CK1δ as well as one apo CK1ε crystal structure. These structures provide a molecular basis for the strong and specific inhibitor interactions with CK1ε and suggest clues for further development of CK1δ inhibitors.
MeSH terms
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Amino Acid Sequence
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Apoenzymes
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Casein Kinase 1 epsilon / chemistry*
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Casein Kinase 1 epsilon / genetics
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Casein Kinase 1 epsilon / metabolism
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Casein Kinase Idelta / chemistry*
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Casein Kinase Idelta / genetics
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Casein Kinase Idelta / metabolism
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Catalytic Domain
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Crystallography, X-Ray
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Humans
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Models, Molecular
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Molecular Sequence Data
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Mutation / genetics
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Protein Conformation
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / metabolism*
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Sequence Homology, Amino Acid
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Structure-Activity Relationship
Substances
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Apoenzymes
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Protein Kinase Inhibitors
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Casein Kinase 1 epsilon
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Casein Kinase Idelta
Associated data
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PDB/4HNF
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PDB/4HNI
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PDB/4HOK