BETA 6 AMINO ACID ON ALPHA & BETA ASSEMBLY TO TETRAMERIC HEMOGLOBIN

α 上的 Beta 6 氨基酸

• 批准号: 6281080
• 负责人: K ADACHI
• 金额: $ 0.05万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6281080
• 关键词: bioengineering /biomedical engineering; biological products; biomedical resource; biotechnology; genetics; hematology; orphan disease /drug; proteins

We are studying the effect of beta-6 amino acid on the alpha and beta assembly to produce tetrameric hemoglobin using time resolved spectroscopy. Hb S usually comprises about 40% if 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 alpha and beta mixing experiments show that alpha-beta A dimers form more readily than the S dimer. The reasons for this are not readily apparent. The beta-6 amino acid is on the surface of the beta chain and far removed from the alpha-1:beta-1 contact region that is critical for the initial formation of alpha beta dimers. We are now able to systematically test the effects of beta-6 amino acid charge and hydrophobicity on assembly of hemoglobin molecules by engineering various mutations at the beta-6 position. These studies may also be important for understanding reasons for higher levels of the Hb S in sickle cell compared to A type red cells. Furthermore, this difference is an important determinant of the clinical manifestations of sickle cell disease.

我们正在研究β-6氨基酸对α和 利用时间分辨的β组装生产四聚体血红蛋白 光谱学。HB S通常占约40%，如果总数 具有镰状细胞特征的个体的红细胞中的血红蛋白。 在持镰刀的人中，与Hb A相比，Hb S的含量较低 细胞特性，拥有完整的阿尔法基因是令人费解的。在……里面 体外α和β混合实验表明，α-βA二聚体 比S二聚体更容易形成。这样做的原因并不是 显而易见的。β-6氨基酸位于β表面。 链，并远离α-1：β-1接触区，即 对α-β二聚体的初始形成至关重要。我们现在是 能够系统地测试β-6氨基酸电荷的影响 和疏水性对血红蛋白分子的工程化组装 β-6位的各种突变。这些研究也可能是 了解S血红蛋白水平偏高的原因 镰状细胞与A型红细胞的比较。此外，这一点 差异是决定临床表现的重要因素 镰状细胞病。