Structural and functional characterization of the human protein kinase ASK1.
|Abstract||Apoptosis signal-regulating kinase 1 (ASK1) plays an essential role in stress and immune response and has been linked to the development of several diseases. Here, we present the structure of the human ASK1 catalytic domain in complex with staurosporine. Analytical ultracentrifugation (AUC) and crystallographic analysis showed that ASK1 forms a tight dimer (K(d) approximately 0.2 microM) interacting in a head-to-tail fashion. We found that the AS ... [truncated at 450 characters in length]|
|Author||Bunkoczi, Gabor; Salah, Eidarus; Filippakopoulos, Panagis; et al|
|Subject||Amino Acid Sequence Binding Sites Catalysis Dimerization Enzyme Activation Enzyme Inhibitors Humans MAP Kinase Kinase Kinase 5 Models, Molecular Molecular Sequence Data Phosphorylation Protein Conformation Protein Structure, Tertiary Staurosporine Structure-Activity Relationship Substrate Specificity chemistry metabolism chemistry metabolism chemistry metabolism|
Structure of the human protein kinase MPSK1 reveals an atypical activation loop architecture.
|Abstract||The activation segment of protein kinases is structurally highly conserved and central to regulation of kinase activation. Here we report an atypical activation segment architecture in human MPSK1 comprising a beta sheet and a large alpha-helical insertion. Sequence comparisons suggested that similar activation segments exist in all members of the MPSK1 family and in MAST kinases. The consequence of this nonclassical activation segment on substra ... [truncated at 450 characters in length]|
|Author||Eswaran, Jeyanthy; Bernad, Antonio; Ligos, Jose M; et al|
|Subject||Amino Acid Sequence Animals Conserved Sequence Enzyme Activation Humans Kinetics Models, Molecular Molecular Sequence Data Protein Conformation Protein-Serine-Threonine Kinases Staurosporine Substrate Specificity Transcription Factors chemistry metabolism metabolism chemistry metabolism|
Crystal structure of the PIM2 kinase in complex with an organoruthenium inhibitor.
|Abstract||The serine/threonine kinase PIM2 is highly expressed in human leukemia and lymphomas and has been shown to positively regulate survival and proliferation of tumor cells. Its diverse ATP site makes PIM2 a promising target for the development of anticancer agents. To date our knowledge of catalytic domain structures of the PIM kinase family is limited to PIM1 which has been extensively studied and which shares about 50% sequence identity with PIM2.|
|Author||Bullock, Alex N; Russo, Santina; Amos, Ann; et al|
|Subject||Binding Sites Chemistry, Pharmaceutical Crystallography, X-Ray Drug Design Enzyme Inhibitors Humans Molecular Structure Protein Conformation Protein Isoforms Protein Structure, Tertiary Proto-Oncogene Proteins c-pim-1 Ruthenium Staurosporine Structure-Activity Relationship methods methods chemistry chemistry chemistry chemistry|