Biochemical Characterization of the CAMKV Pseudokinase

CAMKV 假激酶的生化特征

• 批准号: 10666873
• 负责人: Stefan W. Vetter
• 金额: $ 14.5万
• 依托单位: NORTH DAKOTA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10666873
• 关键词: Affinity; Amino Acids; Antibodies; Binding; Binding Proteins; Binding Sites; Biochemical; Biological; Biological Assay; Brain; C-terminal; Calmodulin; Calorimetry; Catalytic Domain; Central Nervous System; Data; Development; Disease; Enzymes; Foundations; Gene Expression; Genes; Homologous Gene; Human; Immobilization; Ions; Knowledge; Learning; Length; Libraries; Ligand Binding; Ligands; Link; Mass Spectrum Analysis; Measures; Memory; Mental disorders; Methods; Molecular; Molecular Conformation; Mutation; Neurons; Nucleotides; Pathologic; Phosphotransferases; Physiological; Pilot Projects; Play; Post-Traumatic Stress Disorders; Property; Proteins; Proteomics; Psyche structure; Publications; Rattus; Recombinants; Regulation; Research; Role; Signal Transduction; Source; Tail; Thermodynamics; Tissues; Titrations; Transition Temperature; United States National Institutes of Health; Vesicle; brain tissue; cell growth regulation; cognitive function; drug-like compound; experimental study; genome wide association study; human disease; inhibitor; innovation; insight; interest; kinase inhibitor; preservation; protein complex; protein protein interaction; scaffold

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.

CAMKV 是一种脑特异性假激酶，与钙调蛋白调节激酶 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 在精神障碍中的作用，包括创伤后应激障碍。 CAMKV 已 NIH – IDG 倡议将其确定为需要进一步研究的蛋白质。 拟议的研究将有助于 CAMKV 的生化表征 研究其在分子水平上的调控机制。具体目标1，配体 将鉴定针对 CAMKV 退化 ATP 结合袋的目标。预期结果， 将为内源配体对 CAMKV 的细胞调节提供见解，并确定 小药物分子作为潜在的 CAMKV 抑制剂或激活剂。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。了解 CAMKV 目标将是 了解其在正常神经元组织中的作用以及提供 CAMKV 在精神疾病中的作用奠定了基础。