Assignment First

商科代写:HbA突变体Hb Bassett在阿尔法亚基的结构

本研究的主题是讨论HbA突变体Hb Bassett在阿尔法亚基第94位将天冬氨酸单一置换成丙氨酸的结构和功能作用。该突变体首次在“R和t态血红蛋白Bassett的结构”中被发现:阐明结构基础上的低氧亲和力变异血红蛋白”Abdulmalik等人于2004年(5),扰乱了α1β2联系网站发生变异,导致不稳定的含氧R-state,导致降低了合作社,从而降低了氧亲和力(5)。Hb巴也有更高的p50(用于酶活性降低50%,与氧饱和度)相比HbA(血红蛋白)(5)。因此,t态处于平衡状态,Hb Bassett不能有效、充分地输送氧气,导致组织内氧饱和度低(5)。临床疗效方面,Hb Bassett突变患者诊断为青紫病,皮肤呈浅蓝色变色(5)。

商科代写:HbA突变体Hb Bassett在阿尔法亚基的结构

– 1和- 2接触点的局部结构差异和-裂缝

Beta-FG角落转变

-链向阿尔法螺旋靠近

三级和四级结构保持相似(由RMSD值建议)

商科代写:HbA突变体Hb Bassett在阿尔法亚基的结构

The topic of this study is to discuss the structural and functional effects of a mutant variant of HbA, Hb Bassett, with a single substitution of aspartate into alanine at the 94th position of the alpha subunit. This mutant variant was firstly discovered in “Structures of R- and T-state hemoglobin Bassett: elucidating the structural basis for the low oxygen affinity of a mutant hemoglobin” by Abdulmalik et al. in 2004 (5). The mutation disrupts the α1β2 contact site which results in destabilization of the oxygenated R-state, leading to lowered cooperatives and thus lowering oxygen binding affinity (5). Hb Bassett also has a much higher p50 (Used to lower the enzyme activity by 50%which is related to the saturation of oxygen) compared to HbA (Hemoglobin A) (5). As a consequence, T-state is favored in the equilibrium, and Hb Bassett is not able to transport oxygen effectively and sufficiently, leading to low oxygen saturation in tissues (5). As for clinical effects, people with Hb Bassett mutation are diagnosed with cyanosis, which are bluish discoloration of the skin (5).

商科代写:HbA突变体Hb Bassett在阿尔法亚基的结构

Localized structural difference at alpha 1 and beta 2 contact point and beta-cleft
Beta-FG corner shift
Beta-chain shifts closer to the alphaC-helix
Tertiary and quaternary structures remain similar (suggested by RMSD values)