GELATION OF SICKLE HEMOGLOBIN .3. NITROSYL HEMOGLOBIN
GELATION OF SICKLE HEMOGLOBIN .3. NITROSYL HEMOGLOBIN
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DOI：
10.1016/0022-2836(75)90149-7
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发表时间：
1975-01-01
影响因子：
5.6
通讯作者：
SALHANY, JM
中科院分区：
文献类型：
--
作者：
BRIEHL, RW;SALHANY, JM
镰状细胞亚硝基血红蛋白通过先前描述的超离心方法（Briehl & Ewert, 1973）和双折射检查凝胶。在六磷酸肌醇存在的情况下，两种技术都观察到在脱氧血红蛋白S凝胶中出现的吸热温度依赖。在缺乏六磷酸肌醇的情况下，没有观察到凝胶化，亚硝基血红蛋白A也没有表现出凝胶化。假设凝胶化依赖于脱氧或T（低配体亲和力）而不是氧或R（高配体亲和力）的四级结构，这支持了六磷酸肌醇中的亚硝基血红蛋白S具有T结构的结论，与其他配体血红蛋白铁衍生物氧和一氧化碳血红蛋白相反。进一步假设血红蛋白A和血红蛋白S的四级结构和异构化是相同的，也可以得出结论，六磷酸肌醇中的亚硝基血红蛋白A呈T态。由于在剥离的亚硝基血红蛋白S中没有看到凝胶化，因此六磷酸肌醇在该衍生物中起到了R到T转换的作用。因此，在亚硝基血红蛋白中R-T异构化发生时，血红素第6位的配体结合没有改变，这证实了Salhany（1974）和Salhanyet al.（1974）的结论。将pH值降低至6有利于NO血红蛋白S的凝胶化，就像它有利于脱氧和高铁血红蛋白S一样（Briehl & Ewert, 1973,1974），这与由于链间盐桥的加强和六磷酸肌醇的结合以及/或凝胶化所依赖的位点间相互作用的改变而有利于T结构一致。
Sickle cell nitrosyl hemoglobin was examined for gelation by an ultracentrifugal method previously described (Briehl & Ewert, 1973) and by birefringence. In the presence of inositol hexaphosphate gelation which exhibited the endothermic temperature dependence seen in gels of deoxyhemoglobin S was observed by both techniques. In the absence of inositol hexaphosphate no gelation was observed, nor did nitrosyl hemoglobin A exhibit gelation. On the assumption that gelation is dependent on the deoxy or T (low ligand affinity) as opposed to the oxy or R (high ligand affinity) quaternary structure this supports the conclusion that nitrosyl hemoglobin S in inositol hexaphosphate assumes the T structure, in contrast to the other liganded ferrohemoglobin derivatives oxy and carbon monoxide hemoglobin. Assuming further that the quaternary structures and isomerizations are the same in hemoglobins A and S it can also be concluded that nitrosyl hemoglobin A in inositol hexaphosphate assumes the T state. Since no gelation was seen in stripped nitrosyl hemoglobin S, inositol hexaphosphate serves to effect an R to T switch in this derivative. Thus R-T isomerization in nitrosyl hemoglobin occurs without change in ligand binding at the sixth position of the heme group confirming the conclusion of Salhany (1974) and Salhanyet al. (1974).Lowering of the pH toward 6 favors gelation of NO hemoglobin S as it does of deoxy and aquomethemoglobin S (Briehl & Ewert, 1973,1974), consistent with a favoring of the T structure due to strengthening of the interchain salt bridges and the binding of inositol hexaphosphate and/or changes in site-to-site interactions on which gelation depends.