REDESIGN OF CU,ZN SUPEROXIDE DISMUTASE TO PROBE MECHANISM, ELECTROSTA CONTROL,

铜锌超氧化物歧化酶探针机制、Electrosta 控制的重新设计

• 批准号: 6119448
• 负责人: TERRENCE P LO
• 金额: --
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2000-04-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6119448
• 关键词: biomaterials; enzymes; neoplasm /cancer

Cu,Zn superoxide dismutase is a key enzyme in the cellular defense against free radical oxidation. We are carrying out coupled structural and biochemical experiments to probe the contributions of electrostatics, stability, and metal binding to the catalytic mechanism of this enzyme. We have produced mutant proteins with altered electrostatics which either increase or decrease catalytic activity. We have generated other mutants with altered stability. We have also made mutant enzymes with altered metal binding. We will determine the structures of these mutant enzymes to form a basis for interpreting our functional data. These combined results will be important for elucidating the molecular mechanism of neurodegenerative disease (ALS) which has been linked to defects in Cu,Zn superoxide dismutase.

Cu,Zn 超氧化物歧化酶是细胞防御的关键酶 对抗自由基氧化。 我们正在进行耦合 结构和生化实验来探讨的贡献 静电、稳定性和金属与催化剂的结合 这种酶的作用机制。 我们已经生产了突变蛋白 改变静电，增加或减少催化作用 活动。 我们已经产生了稳定性改变的其他突变体。 我们 还制造了具有改变的金属结合的突变酶。 我们将 确定这些突变酶的结构，为 解释我们的功能数据。 这些综合结果将是 对于阐明神经退行性疾病的分子机制具有重要意义 与铜、锌超氧化物缺陷有关的疾病 (ALS) 歧化酶。