Structure and substrate specificity of the Pim-1 kinase.
|Abstract||The Pim kinases are a family of three vertebrate protein serine/threonine kinases (Pim-1, -2, and -3) belonging to the CAMK (calmodulin-dependent protein kinase-related) group. Pim kinases are emerging as important mediators of cytokine signaling pathways in hematopoietic cells, and they contribute to the progression of certain leukemias and solid tumors. A number of cytoplasmic and nuclear proteins are phosphorylated by Pim kinases and may act a ... [truncated at 450 characters in length]|
|Author||Bullock, Alex N; Debreczeni, Judit; Amos, Ann L; et al|
|Subject||Amino Acid Motifs Arginine Binding Sites Biotinylation Calcium-Calmodulin-Dependent Protein Kinase Type 1 Calcium-Calmodulin-Dependent Protein Kinases Calorimetry Cell Nucleus Crystallography, X-Ray Cytoplasm Glycine Hematopoietic Stem Cells Humans Kinetics Models, Molecular Peptide Library Peptide Nucleic Acids Peptides Phosphorylation Protein Binding Protein Conformation Protein Isoforms Protein Structure, Tertiary Protein-Serine-Threonine Kinases Proto-Oncogene Proteins Proto-Oncogene Proteins c-pim-1 Substrate Specificity chemistry metabolism metabolism metabolism chemistry metabolism chemistry chemistry metabolism physiology physiology metabolism physiology|
Structural analysis identifies imidazo[1,2-b]pyridazines as PIM kinase inhibitors with in vitro antileukemic activity.
|Abstract||Much attention has recently been focused on PIM kinases as potential targets for the treatment of hematopoietic malignancies and some solid cancers. Using protein stability shift assays, we identified a family of imidazo[1,2-b]pyridazines to specifically interact with and inhibit PIM kinases with low nanomolar potency. The high-resolution crystal structure of a PIM1 inhibitor complex revealed that imidazo[1,2-b]pyridazines surprisingly interact w ... [truncated at 450 characters in length]|
|Author||Pogacic, Vanda; Bullock, Alex N; Fedorov, Oleg; et al|
|Subject||Animals Antineoplastic Agents Cell Line, Tumor Chemistry, Pharmaceutical Drug Design Enzyme Inhibitors Humans Inhibitory Concentration 50 Mice Models, Chemical Models, Molecular Protein Binding Protein-Serine-Threonine Kinases Proto-Oncogene Proteins Proto-Oncogene Proteins c-pim-1 Pyridazines Structure-Activity Relationship pharmacology methods chemistry pharmacology antagonists and inhibitors antagonists and inhibitors chemistry|
Activation segment exchange: a common mechanism of kinase autophosphorylation?
|Abstract||The crystal structure of the kinase domain from human checkpoint kinase 2 (Chk2) has shown, for the first time, the reciprocal exchange of activation segments between two adjacent molecules and provides the molecular basis for understanding the observed mode of Chk2 kinase activation via trans-autophosphorylation. With further examples of activation segment exchanged kinase domains now publicly available (i.e. Ste20-like kinase, Ser/Thr kinase 10 ... [truncated at 450 characters in length]|
|Author||Oliver, Antony W; Knapp, Stefan; Pearl, Laurence H;|
|Subject||Animals Crystallography, X-Ray Dimerization Humans Models, Biological Models, Chemical Molecular Conformation Phosphorylation Protein Conformation Protein Structure, Tertiary Protein-Serine-Threonine Kinases Serine Threonine methods chemistry metabolism physiology chemistry chemistry|
Structure and regulation of the human Nek2 centrosomal kinase.
|Abstract||The dimeric Ser/Thr kinase Nek2 regulates centrosome cohesion and separation through phosphorylation of structural components of the centrosome, and aberrant regulation of Nek2 activity can lead to aneuploid defects characteristic of cancer cells. Mutational analysis of autophosphorylation sites within the kinase domain identified by mass spectrometry shows a complex pattern of positive and negative regulatory effects on kinase activity that are ... [truncated at 450 characters in length]|
|Author||Rellos, Peter; Ivins, Frank J; Baxter, Joanne E; et al|
|Subject||Allosteric Regulation Binding Sites Centrosome Crystallography, X-Ray DNA Mutational Analysis Dimerization Humans Mass Spectrometry Phosphorylation Protein-Serine-Threonine Kinases enzymology antagonists and inhibitors chemistry|
Crystal Structures of the p21-activated kinases PAK4, PAK5, and PAK6 reveal catalytic domain plasticity of active group II PAKs.
|Abstract||p21-activated kinases have been classified into two groups based on their domain architecture. Group II PAKs (PAK4-6) regulate a wide variety of cellular functions, and PAK deregulation has been linked to tumor development. Structural comparison of five high-resolution structures comprising all active, monophosphorylated group II catalytic domains revealed a surprising degree of domain plasticity, including a number of catalytically productive an ... [truncated at 450 characters in length]|
|Author||Eswaran, Jeyanthy; Lee, Wen Hwa; Debreczeni, Judit E; et al|
|Subject||Amino Acid Sequence Animals Catalytic Domain Crystallography Molecular Sequence Data Protein Conformation Protein Kinase Inhibitors Protein-Serine-Threonine Kinases Purines drug effects genetics chemistry pharmacology antagonists and inhibitors chemistry genetics chemistry|