Pagnier J, Baudin-Chich V, Lacaze N, Bohn B, Poyart C
INSERM U299 Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.
Br J Haematol. 1990 Apr;74(4):531-4. doi: 10.1111/j.1365-2141.1990.tb06346.x.
The doubly substituted variant Hb S-Antilles (beta 6 Glu----Val, beta 23 Val----Ile) produces sickling in heterozygous carriers. The Csat value for pure deoxyHb S-Antilles is nearly half that of deoxyHb S. Dilute solutions of pure Hb S-Antilles have a lower oxygen affinity than those of Hb A or Hb S. The mutant Hb alpha 2 beta 2 23 Val----Ile was synthesized in E. coli. It exhibits a decreased oxygen affinity compared to Hb A and does not polymerize in 1.8 M phosphate buffer. Mixtures of equal amounts of Hb S + Hb beta 23 Val----Ile have a decreased Csat value compared to mixtures of Hb S + Hb A. The beta 23 Val in Hb S contributes to the axial contact joining molecules in each single filament. Substituting Ile for Val at this site increases the strength of this contact through hydrophobic interactions, allowing increased stability of the lateral contact between filaments in pair, which is the specific unit structure of polymers in deoxyHb S.
双重取代变体血红蛋白 S - 安的列斯（β6 谷氨酸→缬氨酸，β23 缬氨酸→异亮氨酸）在杂合子携带者中会导致镰状化。纯脱氧血红蛋白 S - 安的列斯的 Csat 值几乎是脱氧血红蛋白 S 的一半。纯血红蛋白 S - 安的列斯的稀溶液比血红蛋白 A 或血红蛋白 S 的氧亲和力更低。突变型血红蛋白α2β2 23 缬氨酸→异亮氨酸在大肠杆菌中合成。与血红蛋白 A 相比，它表现出降低的氧亲和力，并且在 1.8 M 磷酸盐缓冲液中不发生聚合。与血红蛋白 S + 血红蛋白 A 的混合物相比，等量的血红蛋白 S + 血红蛋白β23 缬氨酸→异亮氨酸的混合物的 Csat 值降低。血红蛋白 S 中的β23 缬氨酸有助于每条单丝中连接分子的轴向接触。在此位点用异亮氨酸取代缬氨酸通过疏水相互作用增加了这种接触的强度，使得双丝中丝之间横向接触的稳定性增加，这是脱氧血红蛋白 S 中聚合物的特定单位结构。
