ANION DEPENDENT PROPERTIES OF TRANSFERRIN

转铁蛋白的阴离子依赖性特性

• 批准号: 3269922
• 负责人: NORMAN D. CHASTEEN
• 金额: $ 11.75万
• 依托单位: UNIVERSITY OF NEW HAMPSHIRE
• 依托单位国家: 美国
• 财政年份: 1975
• 资助国家: 美国
• 起止时间: 1975-06-01 至 1987-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3269922
• 关键词: adenosine triphosphate; computer simulation; electron spin resonance spectroscopy; human tissue; ligands; mathematical model; metalloproteins; nuclear magnetic resonance spectroscopy; radiotracer; stable isotope; stereochemistry; transferrin; vanadium

The transferrins are a class of important proteins which transport metabolic iron. These proteins reversibly bind two moles of iron but in order to do so a suitable anion must also bind to the protein. Little is known about the structure of the metal and anion binding sites or the mechanism of release or uptake of iron by human serotransferrin. The research proposed here addresses these important questions. The metal and anion binding sites will be characterized by using EPR and NMR spectroscopy of various anion and metal, e.g., Cu(II), and VO(II), and Fe(III), derivatives of the protein. This information will be used to construct a model for the coordination about the metal. It will be determined which ligands are labile and hence important for metal ion release. In particular, the possible role of coordinated water will be examined through NMR spectroscopy and kinetic studies. The mechanism of action of various agents such as ATP or citrate which facilitate iron release by human serotransferrin, will be studied kinetically and spectroscopically. NMR will be employed to map distances between various binding sites relative to the metal center. The structural requirement of the anion and the fundamental nature of its interaction with the protein will be studied in detail. The possible significance of secondary anion binding sites to the action of the transferrin will be determined. The catalytic effect of other metal ions on the release of iron from human serotransferrin will be evaluated as possible mechanism of iron release. This comprehensive study should lead to a better understanding of the mechanism of uptake, transport, and release of metabolic iron by human serotransferrin, and the role that metal site structure, anions, ATP, and other factors play in such processes.

转铁蛋白是一类重要的转运代谢蛋白