SICKLE HEMOGLOBIN PATHOPHYSIOLOGY--STRUCTURES AND KINETICS

镰状血红蛋白病理生理学——结构和动力学

• 批准号: 6110865
• 负责人: FRANK A FERRONE
• 金额: --
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6110865
• 关键词: chemical kinetics; clinical research; dichroism; erythrocyte membrane; hemoglobin Ss; human subject; ligands; oxygen tension; phlebotomy; polymerization; protein structure function; spectrin; thermodynamics

This project addresses three separate issues related to the kinetics of HbS polymerization and the formation of domains. The three principle issues are: (1) the effect of components of the red cell on homogenous nucleation; (2) the effect of domain formation on mass distribution of both polymerized and free HbS in the gelled sample and (3) the effects of the subunit tertiary structure on the thermodynamics and kinetics of polymerization. Ferrone lists three specific aims in this project A.)Measurements of the homogenous nucleation rates of HbS in the presence of membrane preparations including inside-out vesicles of Hb A and Hb S cells with and without spectrin. Any preparation in which effects are observed in the initial observations will be subjected to detailed studies. B.) Polymer domain formation will be studied in a series of hemoglobins prepared by site directed mutagenesis. C) Double mutant models for partially liganded hemoglobins (e.g. Hb S/M Hyde Park or partially saturated NOHbS) will be characterized kinetically and thermodynamically in dilute and in concentrated solutions.

该项目解决了与动力学有关的三个单独的问题 HBS聚合和域的形成。这三个原则 问题是：（1）红细胞组成部分对均匀的影响 成核； （2）域形成对质量分布的影响 胶凝样品中的聚合和游离HBS和（3） 热力学和动力学的亚基三级结构 聚合。 Ferrone在该项目中列出了三个特定目标。）测量 在膜存在下HBS的同质成核速率 带有HB A和HB S细胞内外囊泡的制剂和 没有光谱。任何在观察到效果的准备工作 最初的观察将受到详细研究。 B.）聚合物 域形成将在一系列由由 站点定向诱变。 c）部分配体的双重突变模型 血红蛋白（例如HB S/M Hyde Park或部分饱和的NOHB）是 在稀释和热力学上以稀释和热力学的特征 集中溶液。