CAMK2B + inhibitor
CAMK2B + inhibitor: Human calcium/calmodulin-dependent protein kinase (CaM kinase) II beta + inhibitor
PDB Code: 3BHH
The protein kinase CAMK2β is highly expressed in endocrine tissues such as adrenals, pituitary and beta cells and moderately expressed in the liver. Low levels of expression have also been reported in lymphocytes, adipose tissue, muscle, primary fibroblasts and in primary osteoblasts. The full length protein is organized in an oligomeric, ring like structures composed of 6-12 subunits. There are four isoforms present in mammalian cells (alpha, beta, gamma, and delta).
By functioning as a local calcium sensor, CAMK2β exerts a critical influence on the architecture of the developing brain. The enzyme plays an important role in long-term potentiation and neurotransmitter release, in regulating unitary synaptic strength as well as mEPSC frequency and it may play a role in maturation and plasticity of synapses. In addition, CAMK2β serves as a structural protein that organizes F-actin required for the maintenance of the postsynaptic architecture of the dendritic spine. A role of CAMK2β has also been suggested as a platelet-activating factor, regulating sperm motility and insulin secretion from pancreatic beta-cells.
Low expression levels of CAMK2β have been described in a variety of tumor cells but new tumor specific transcripts have been described. An important function of CAMK2β has been discussed in pathways that lead to evasion of apoptosis under androgen ablation in prostate cancer cells and in facilitating the progression to an androgen independent state. In addition, expression of CAMK2β is elevated in brain tissue of patients suffering form schizophrenia or depression and may contribute to these diseases by influencing the expression of many neuroreceptors, neural outgrowth and pruning. Here we present the structure of the kinase domain of CAMK2β in complex with an ATP competitive inhibitor.
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