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PRIMARY AND SECONDARY BINDING SITES OF THE TRANSFERRINS

转铁蛋白的主要和次要结合位点

基本信息

批准号：
3225866
负责人：
GEORGE W BATES
金额：
$ 12.97万
依托单位：
TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
依托单位国家：
美国
项目类别：
财政年份：
1977
资助国家：
美国
起止时间：
1977-12-01 至 1989-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3225866
关键词：
bioassay chelation therapy erythrocytes ferritin gel filtration chromatography hemoglobin hemoprotein metabolism intracellular ion transport iron metabolism membrane permeability mitochondria polysomes radiotracer reticulocytes transferrin

项目摘要

The Research Plan can be divided into five sections. 1. Secondary metal binding sites of sero- and lactotransferrin. Evidence from amino acid sequence comparisons, EPR, kinetics and spectrophotometry reveal the presence of secondary metal binding sites. I wish to ascertain their stoichiometry, relative affinities for different metals, metal exchange reactivities and their effect on the primary metal/anion sites. 2. Iron exchange reactivities of lactotransferrin. Little is known about the reactions in which lactotransferrin attacks, sequesters and releases iron. This information will shed light on possible physiological roles of lactotransferrin and provide a valuable comparison with the data on serotransferrin. 3. Environmental and chemical modification and the iron exchange reactivities of the transferrins. Denaturants, pH, chemical modification, temperature and salts have a differential effect on the sites in the transferrins' two lobes. I want to know how the modification alters the attack, sequestration and iron release properties. Of special interest will be insight into the conformational change that results in the labilization of the iron and anion binding stress. 4. Control of attack, sequestration and release of iron by the anion binding site. The anion binding site controls the affinity of the protein for iron and other metals. This phenomenon can be explored via the use of carbonate substitutes in studies of metal ion attack, sequestration, oxidation, reduction and release. 5. Exchange of metals other than iron by the transferrins. The transferrins offer an excellent model system for examining protein metal ion exchange for Cu, Mn, Co, Cr, Ni and others. I want to discover the rules that govern exchange of metal ions and to learn about the mechanisms that direct metals to specific sites. 6. Metal ion exchange between the transferrins and other proteins. How are metal ions passed from one protein to another? Is it always via mediators such as chelators and redox reagents? or via a modification force such as acidification? Do protein-metal-protein complexes form? Ceruloplasmin, phosvitin, the sero-, ovo- and lactotransferrins, serum albumin, carboxypeptidase A, ferritin will be subjects of study. 7. Lactotransferrin in milk and serotransferrin in serum. Too little attention is paid to the metal ion exchange reactivities in the natural environment. I wish to extend much of the work above to the physiological media of interest.

研究计划可分为五个部分。 1. 血清转铁蛋白和乳转铁蛋白的次要金属结合位点。证据来自氨基酸序列比较、EPR、动力学和分光光度法揭示次生金属结合位点的存在。我想确定它们的化学计量、对不同金属的相对亲和力、金属交换反应性及其对主要金属/阴离子位点的影响。 2.乳转铁蛋白的铁交换反应性。鲜为人知的是乳转铁蛋白攻击、隔离和释放的反应铁。这些信息将揭示以下物质可能的生理作用：乳转铁蛋白，并与以下数据进行有价值的比较血清转铁蛋白。 3. 环境和化学改性与铁转铁蛋白的交换反应性。变性剂、pH、化学品改性、温度和盐对位点有不同的影响在转铁蛋白的两个叶中。我想知道修改后如何改变攻击、隔离和铁释放特性。特别感兴趣将深入了解导致的构象变化铁和阴离子结合应力的不稳定。 4.控制攻击，通过阴离子结合位点螯合和释放铁。负离子结合位点控制蛋白质对铁和其他物质的亲和力金属。这种现象可以通过使用碳酸盐来探索金属离子攻击、螯合、氧化研究中的替代品，减少和释放。 5. 铁以外的金属的交换转铁蛋白。转铁蛋白提供了一个优秀的模型系统检查蛋白质金属离子交换的铜、锰、钴、铬、镍等。我想要发现控制金属离子交换的规则并学习关于将金属引导至特定位点的机制。 6.金属离子转铁蛋白和其他蛋白质之间的交换。金属离子如何从一种蛋白质传递到另一种蛋白质？是否总是通过中介，例如螯合剂和氧化还原试剂？或通过修改力，例如酸化？蛋白质-金属-蛋白质复合物会形成吗？铜蓝蛋白，卵黄高磷蛋白、血清转铁蛋白、卵转铁蛋白和乳转铁蛋白、血清白蛋白、羧肽酶A、铁蛋白将是研究对象。 7. 牛奶中的乳转铁蛋白和血清中的血清转铁蛋白。太少了自然界中的金属离子交换反应受到关注环境。我希望将上述大部分工作扩展到生理学领域感兴趣的媒体。