Huisman T H, Brown A K, Efremov G D, Wilson J B, Reynolds C A, Uy R, Smith L L
J Clin Invest. 1971 Mar;50(3):650-9. doi: 10.1172/JCI106535.
An abnormal hemoglobin, termed Hb Savannah, was found in red cell hemolysate of a young Caucasian girl with severe hemolytic anemia. The presence of this unstable variant became evident when inclusion bodies appeared rapidly upon exposure of red cells to redox dyes and a large percentage of hemoglobin in hemolysate precipitated on warming to 65 degrees C. Treatment of the hemoglobin with p-hydroxymercuribenzoate (PMB) caused a rapid dissociation into monomers; starch-gel electrophoresis of PMB-treated hemoglobin showed the presence of abnormal beta-chains. Data from structural studies of isolated beta-chains indicated substitution of a valyl residue for the normally occurring glycyl residue at position 24, which corresponds to helical residue B6. A similar substitution but with an arginine replacing the glycyl residue has been observed in Hb Riverdale-Bronx. The glycine to valine substitution will change the relationship of the B and the E helices which results in extensive conformational changes in the beta-chain. This change presumably causes an increased dissociation of the hemoglobin molecule into dimers and probably monomers, and a decreased stability of the alphabeta-dimers. The hemoglobin abnormality may be the result of a fresh mutation because the abnormality is not present in the parents nor in any of the seven siblings.
在一名患有严重溶血性贫血的年轻白种女孩的红细胞溶血产物中，发现了一种异常血红蛋白，称为Hb Savannah。当红细胞暴露于氧化还原染料时，包涵体迅速出现，且溶血产物中的大部分血红蛋白在加热至65摄氏度时沉淀，此时这种不稳定变体的存在变得明显。用对羟基汞苯甲酸（PMB）处理血红蛋白会使其迅速解离成单体；经PMB处理的血红蛋白的淀粉凝胶电泳显示存在异常的β链。对分离出的β链进行结构研究的数据表明，在对应于螺旋残基B6的第24位，一个缬氨酰残基取代了正常存在的甘氨酰残基。在Hb Riverdale-Bronx中观察到了类似的取代，但取代的是精氨酸而非甘氨酰残基。甘氨酸被缬氨酸取代会改变B螺旋和E螺旋的关系，从而导致β链发生广泛的构象变化。这种变化可能会导致血红蛋白分子更多地解离成二聚体，甚至可能是单体，同时αβ二聚体的稳定性降低。这种血红蛋白异常可能是新突变的结果，因为父母及七个兄弟姐妹中均未出现这种异常。
