BETA 6 AMINO ACID: ALPHA & BETA ASSEMBLY TO PRODUCE TETRAMERIC HEMOGLOBIN

Beta 6 氨基酸：阿尔法

• 批准号: 6480826
• 负责人: K ADACHI
• 金额: $ 15.58万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6480826
• 关键词: biological products; biomedical resource; proteins

We are studying the effect of ?-6 amino acid on the ? and ? assembly to produce tetrameric hemoglobin using time resolved spectroscopy. Hb S usually comprises about 40% of the total hemoglobin in the red cells of individuals with sickle cell trait. This lesser amount of Hb S compared to Hb A in persons with sickle cell trait, having a full complement of alpha genes is puzzling. In vitro ? and ? mixing experiments show that ?-? A dimers form more readily than the S dimer. The reasons for this are not readily apparent. The ?-6 amino acid is on the surface of the ? chain and far removed from the ?-1?-1 contact region that is critical for the initial formation of ??? dimers. We are now able to systematically test the effects of ?-6 amino acid charge and hydrophobicity on assembly of hemoglobin molecules by engineering various mutations at the ?-6 position. These studies will be important for understanding reasons for higher levels of the Hb S in sickle cell compared t o A type red cells. Furthermore, this difference is an important determinant of the clinical manifestations of sickle cell disease.

我们在研究？- 6氨基酸对吗？然后呢？ 使用时间分辨的组装来生产四聚体血红蛋白 谱 Hb S通常占总量的40%左右。 血红蛋白在红细胞的个人镰状细胞性状。 与镰状患者的Hb A相比，Hb S的含量较低 细胞性状，拥有完整的阿尔法基因是令人费解的。 在 试管？然后呢？混合实验表明，？ A二聚体形成更多 比S二聚体更容易。 这其中的原因并不容易理解。 很明显 什么？- 6个氨基酸是在表面的？链和远 从？-一号？1个接触区域，这对于 最初的形成？二聚体。 我们现在能够系统地 测试的效果？6个氨基酸的电荷和疏水性 血红蛋白分子的组装通过工程化的各种突变， 那个？六号位。 这些研究对于理解 镰状细胞中Hb S水平高于A的原因 型红细胞。 此外，这种差异是一个重要的 镰状细胞病临床表现的决定因素。