HEMOGLOBIN STRUCTURE-FUNCTION & BLOOD SUBSTITUTE DESIGN

中心目标是更好地了解这些因素和 控制人类血红蛋白功能行为的元件 分子。将采用的方法是确定以下角色 氨基酸侧链在分子的正常功能中的残基 在特定目标位置的替换加上广泛的 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，这些小组有 相互补充的专业领域和共同感兴趣的重点 血红蛋白功能和结构的机制。为了实现这一目标 集中努力，有必要将个人聚集在一起 来自多个不同的机构。(我们不知道有哪一家机构 在这一领域具有同等水平的兴趣和专业知识。)这 集团在以下方面拥有卓有成效的合作记录 这笔赠款的前一期。其他优势包括：a)高效 在当前环境下开发的运作核心设施 该计划项目的资金用于生产大量的 基因工程血红蛋白变种。B)设施和专门知识 对于结构(即，x射线， 光谱和理论)和功能(动力学和热力学) 血红蛋白的性质。 不同实验室的工作将通过计划进行协调 协作、物质和人员交流，以及季度 开会。结果将被合成到预测模型中 血红蛋白机制。这种新的理解水平可能会允许 结构修饰血红蛋白的合理设计 性能，包括潜在的红细胞替代材料。

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.