Biochemical Characterization of the CAMKV Pseudokinase

CAMKV是一种脑特异性的假激酶，与钙调蛋白调节的激酶1密切相关 (CAMK1)。基因表达研究和全基因组关联研究表明可能的作用 CAMKV在精神障碍，包括创伤后应激障碍中的作用。CAMKV已经被 被NIH-IDG倡议确定为一种需要进一步研究的蛋白质。 拟议的研究将有助于CAMKV的生化特性，通过 从分子水平探讨其调控机制。在特定目标1中，配体 以CAMKV退化的ATP结合口袋为靶点将被识别。预期结果， 将为内源性配体对CAMKV的细胞调控提供见解，并识别 作为潜在的CAMKV抑制剂或激活剂的类药物小分子。在具体目标2中，CAMKV 相互作用的蛋白质将从脑组织中分离出来。CAMKV目标的知识将是 对于理解它在正常神经元组织中的作用以及提供一种 CAMKV在精神疾病中的作用基金会。

CAMKV is a brain specific pseudokinase and closely related to calmodulin regulated kinase 1 (CAMK1). Gene expression studies and genome wide association studies suggest a possible role of CAMKV in mental disorders, including post-traumatic stress disorder. CAMKV has been identified by the NIH – IDG initiative as a protein in need for additional research. The proposed research will contribute to the biochemical characterization of CAMKV by investigating its mechanism of regulation on the molecular level. In specific aim 1, ligands targeting the degenerated ATP binding pocket of CAMKV will be identified. Expected results, will provide insights in the cellular regulation of CAMKV by endogenous ligands and also identify small-drug like molecules as potential CAMKV inhibitors or activators. In specific aim 2, CAMKV interacting proteins will be isolated from brain tissue. Knowledge of CAMKV targets will be critically important to understand its role in normal neuronal tissue, as well as to provide a foundation for the role of CAMKV in mental diseases.