title: Structural basis for the potent and selective inhibition of casein kinase 1 epsilon.
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.
authors.affiliation: Department of Molecular Structure and Characterization, Amgen Inc., 360 Binney Street, Cambridge, Massachusetts 02142, USA.
authors.forename: Alexander M
authors.initials: AM
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; D048149:Casein Kinase 1 epsilon / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D048148:Casein Kinase Idelta / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
chemical_list: D001051:Apoenzymes; D047428:Protein Kinase Inhibitors; D048149:Casein Kinase 1 epsilon; D048148:Casein Kinase Idelta