title: Structural basis for the interaction between casein kinase 1 delta and a potent and selective inhibitor.
abstract: 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.
authors.affiliation: Department of Molecular Structure, Amgen Inc., 360 Binney Street, Cambridge, Massachusetts 02142, United States.
authors.forename: Alexander
authors.initials: A
authors.lastname: Long
authors.forename: Huilin
authors.initials: H
authors.lastname: Zhao
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
mesh_terms: D000595:Amino Acid Sequence; D001051:Apoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry; D048149:Casein Kinase 1 epsilon / Q000037:antagonists & inhibitors / Q000737:chemistry; D048148:Casein Kinase Idelta / Q000037:antagonists & inhibitors* / Q000737:chemistry; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011743:Pyrimidines / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D001051:Apoenzymes; D007093:Imidazoles; D008024:Ligands; D011743:Pyrimidines; C522839:PF-670462; D048149:Casein Kinase 1 epsilon; D048148:Casein Kinase Idelta