Oxygenation-linked subunit interactions in human hemoglobin: analysis of linkage functions for constituent energy terms.
Oxygenation-linked subunit interactions in human hemoglobin: analysis of linkage functions for constituent energy terms.
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人类血红蛋白中氧合连接的亚基相互作用：成分能量项的连接函数分析。
DOI：
10.1021/bi00669a024
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发表时间：
1976
期刊：
影响因子：
2.9
通讯作者：
G. K. Ackers
中科院分区：
文献类型：
--
作者：
M. Johnson;H. Halvorson;G. K. Ackers
通过数值模拟和最小二乘分析，探索了将人血红蛋白中的氧合和亚基缔合-解离平衡之间的联系函数解析为微观组成项。为了优化分辨率，我们使用多种参数集选择来研究参数之间的相关性。研究发现，在当前可用的实验精度水平和变量范围的情况下，两种联动函数都无法提供所有所需能量项的足够分辨率。最难解析的量始终包括未配体血红蛋白的二聚体-四聚体缔合常数和alphabeta二聚体的氧结合常数。克服这些困难的可行的实验策略在于独立测定未配体和完全氧合的血红蛋白的二聚体-四聚体缔合常数。这些常数与中位配体浓度相结合，提供了四聚体总氧化能量的估计，该能量基本上独立于其他组成能量。结果表明，如果这些可单独确定的参数是固定的，则可以使用表示任一联动函数的数据来以良好的精度估计剩余项。一般来说，需要结合来自两种类型的实验量的信息。之前的一篇论文（Mills, F.C.、Johnson, M.L. 和 Ackers, G.K. (1976), Biochemestry, 15，本期的前一篇论文）描述了该策略的实验实施。
Resolution of the linkage functions between oxygenation and subunit association-dissociation equilibria in human hemoglobin into the constituent microscopic terms has been explored by numerical simulation and least-squares analysis. The correlation properties between parameters has been studied using several choices of parameter sets in order to optimize resolution. It is found that, with currently available levels of experimental precision and ranges of variables, neither linkage function can provide sufficient resolution of all the desired energy terms. The most difficult quantities to resolve always include the dimer-tetramer association constant for unliganded hemoglobin and the oxygen binding constants to alphabeta dimers. A feasible experimental strategy for overcoming these difficulties lies in independent determination of the dimer-tetramer association constants for unliganded and fully oxygenated hemoglobin. These constants, in combination with the median lignad concentration, provide an estimate of the energy for total oxygenation of tetramers which is essentially independent of the other constituent energies. It is shown that if these separately determinable parameters are fixed, the remaining terms may be estimated to good accuracy using data which represents either linkage function. In general it is desirable to combine information from both types of experimental quantities. A previous paper (Mills, F.C., Johnson, M.L., and Ackers, G.K. (1976), Biochemestry, 15, the preceding paper in this issue) describes the experimental implementation of this strategy.