PEROXYNITRITE MODIFICATION OF ENZYMES

酶的过氧亚硝酸盐改性

• 批准号: 6290352
• 负责人: EARL R STADTMAN
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6290352
• 关键词: Escherichia coli; biological signal transduction; carbon dioxide; cytotoxicity; enzyme activity; free radical oxygen; glutamate ammonia ligase; nitric oxide; nitrites; nitro compounds; oxidation; peroxides; protein structure function; superoxides; tyrosine

Cellular damage to lipids, proteins, and nucleic acids by endogenously generated peroxynitrite is associated with a number of neurological diseases. Results of earlier studies in this laboratory demonstrated that the ability of peroxynitrite to damage proteins is strongly dependent upon the hydrogen ion concentration and physiological levels of carbon dioxide and that it probably does not contribute significantly to formation of protein carbonyl derivatives or to the oxidation of methionine residues, both of which are widely used markers of oxidative protein damage. In continuing studies to identify major targets for peroxynitrite-dependent modification of proteins, the ability of peroxynitrite to nitrate tyrosine residues in bovine serum albumin (BSA) and glutamine synthetase (GS) was determined. Although these two proteins contain nearly identical numbers of tyrosine residues per subunit, they exhibit markedly different pH-dependent profiles of peroxynitrite-dependent nitration. It is thus evident that nitration of protein tyrosine residues is strongly dependent upon the molecular distribution of tyrosine residues and protein conformation. - peroxynitrite, protein carbonyls, peroxynitrite-carbon dioxide adducts

内源性过氧亚硝酸盐对脂质、蛋白质和核酸的细胞损伤与许多神经系统疾病有关。本实验室早期研究的结果表明，过氧亚硝酸盐损伤蛋白质的能力强烈依赖于氢离子浓度和二氧化碳的生理水平，并且它可能不会显著促进蛋白质羰基衍生物的形成或甲硫氨酸残基的氧化，这两者都是广泛使用的氧化蛋白质损伤的标志物。在继续的研究，以确定过氧亚硝酸盐依赖性修饰的蛋白质的主要目标，过氧亚硝酸盐的能力，硝酸酪氨酸残基在牛血清白蛋白（BSA）和谷氨酰胺合成酶（GS）进行了测定。虽然这两种蛋白质含有几乎相同数量的酪氨酸残基每个亚基，它们表现出显着不同的pH值依赖的过氧亚硝酸盐依赖的硝化。因此，很明显，蛋白质酪氨酸残基的硝化强烈依赖于酪氨酸残基的分子分布和蛋白质构象。- 过氧亚硝酸根、蛋白质羰基、过氧亚硝酸根-二氧化碳加合物