HEMOGLOBIN STRUCTURE-FUNCTION & BLOOD SUBSTITUTE DESIGN

血红蛋白结构-功能

• 批准号: 2227593
• 负责人: Gary K Ackers
• 金额: $ 108.17万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2227593
• 关键词: blood /plasma substitute; hemoglobin; hemoprotein structure; protein structure function

The central goal is to develop a better understanding of the factors and elements which control functional behavior of the human hemoglobin molecule. The approach that will be employed is to identify the roles of amino acid side chains in the molecule's normal functioning by residue substitution at specifically targeted sites coupled with extensive structural and functional characterization of the resulting hemoglobin molecules. This Program Project brings together seven research groups that have complementary areas of expertise and a common focus of interest on mechanisms of hemoglobin function and structure. In order to achieve this concentrated effort, it has been necessary to bring together individuals from a number of different institutions. (We know of no single institution with a comparable level of interest and expertise in this field.) This group has a proven track record of productive collaboration during the previous period of this grant. Other strengths include: a) efficiently functioning core facilities that have been developed under the current funding of this Program Project for production of large amounts of genetically engineered hemoglobin variants. b) Facilities and expertise for detailed, systematic characterization of structural (i.e., x-ray, spectroscopic, and theoretical) and functional (kinetic and thermodynamic) properties of hemoglobin. Work in the different laboratories will be coordinated through planned collaborations, exchanges of materials and personnel, and quarterly meetings. Results will be synthesized into a predictive model of the hemoglobin mechanism. This new level of understanding may permit the rational design of structurally-modified hemoglobins with desired properties, including potential red cell substitute materials.

中心目标是更好地了解因素和 控制人血红蛋白功能行为的元素 分子。将采用的方法是确定 分子正常功能中的氨基酸侧链通过残基的正常功能 在特定针对的站点上取代和广泛的位置 所得血红蛋白的结构和功能表征 分子。 该计划项目汇集了七个研究小组 互补的专业知识领域和共同关注的重点 血红蛋白功能和结构的机制。为了实现这一目标 集中精力，有必要将个人聚集在一起 来自许多不同机构。 （我们知道没有一个机构 在这一领域具有可比的兴趣和专业知识。） 小组在企业合作期间有一个可靠的往绩记录 这笔赠款的前期。其他优势包括：a）有效 在当前开发的功能核心设施 该计划项目的资金用于生产大量 基因设计的血红蛋白变体。 b）设施和专业知识 用于详细的，系统的结构表征（即X射线， 光谱和理论）和功能（动力学和热力学） 血红蛋白的特性。 不同实验室的工作将通过计划进行协调 合作，材料和人员交流以及季度 会议。结果将合成为一个预测模型 血红蛋白机制。这种新的理解水平可能允许 与所需的结构修饰血红蛋白的合理设计 特性，包括潜在的红细胞替代材料。