Normal coordinate structural decomposition of the heme distortions of hemoglobin in various quaternary states and bound to allosteric effectors.
Normal coordinate structural decomposition of the heme distortions of hemoglobin in various quaternary states and bound to allosteric effectors.
复制标题
各种四元状态下的血红蛋白血红素畸变的正常坐标结构分解并与变构效应器结合。
DOI：
10.1023/b:modi.0000006532.16981.e8
复制
发表时间：
2003
影响因子：
3.8
通讯作者：
Fidy,Judit
中科院分区：
文献类型：
--
作者：
Laberge,Monique;Yonetani,Takashi;Fidy,Judit
利用CHARMM能量最小化模型进行正坐标结构分解（NSD）分析，研究了人血红蛋白(HbA) α1、α2、β1和β1血红素在不同季态及变构效应物存在下的畸变。将NSD应用于从HbA的R、T和r2状态模型中提取的单个血红素，以及与DPG和IHP结合的HbA。总的来说，NSD结果不仅表明了不同HbA季态的血红素的特征扭曲，而且表明了与变构效应体结合的HbA模型的血红素的特征扭曲。比较了t态HbA中不等价α和β血红素的畸变，我们发现NSD与文献中报道的α和β HbA血红素的低频ν52（Eg）和γ7（A2u）模式之间存在良好的相关性，同时注意到这些类型的b2和b1畸变之间存在实质性差异。对于R2血红素，NSD产生的血红素扭曲与r态的血红素扭曲更相似，尤其是在量级上。然而，R2血红素并没有表现出α和β血红素扭曲的不平等，这一结果可能有助于理解这种状态的功能重要性。相对于t态血红素扭曲，NSD对效应结合血红素的研究结果表明，由于结合DPGand IHP而引起的t态HbA的三级变化极大地影响了血红素扭曲。在从HbA-DPG模型中提取的α血红素中，最值得注意的是wav(x)和wav(y)畸变的增加以及畸变的增强。在β血红素中，随着浓度的增加，受畸变影响最大的是波(y)。HbA-IHP模型的NSD结果也有所不同，随着α血红素中圆顶的增加，β的变形和变形更加增强。我们的研究结果描述了微妙的蛋白质诱导变化对HbA血红素的非平面性的影响，这可能在调节它们的氧亲和力中起作用。
The distortions of the α1, α2, β1, and β1hemes of human hemoglobin (HbA) in various quaternary states and as affected by the presence of allosteric effectors was investigated by subjecting CHARMM energy-minimized models to normal coordinate structural decomposition (NSD) analysis. NSD was applied to the individual hemes extracted from the R, T, and R2-state models of HbA and to HbA bound to DPG and to IHP. Overall, NSD results are indicative of characteristic distortions, not only for the hemes of the different HbA quaternary states, but also for the hemes of the HbA models bound to allosteric effectors. Comparing the distortions of the inequivalent α and β hemes in T-state HbA, we show good correlation between NSD and the experimentally observed low-frequency ν52(Eg) and γ7(A2u) modes reported in the literature for α and β HbA hemes while noting substantialdifferences between these types for B2uand B1udistortions. For the R2 hemes, NSD yields heme distortions that are more comparableto those of the R-state, especially in magnitude. However, the R2 hemes do not exhibit inequivalence of α and β heme distortions, a result that may contribute to an understanding of the functional importance of this state. Relative to T-state heme distortions, NSD results on the effector-bound hemes show that tertiary changes induced in T-state HbA as a result of binding DPGand IHP drastically affect heme distortions. In the α hemes extracted from the HbA-DPG model, most noteworthy are the increasedwav(x)andwav(y)distortions and enhancement ofrufanddomdeformations. In the β hemes, thewav(y)is the most affected distortion with increase insad. The NSD results are also different for the hemes of the HbA-IHP model, in that the βsadandrufdeformations are more enhanced with increase of doming in the α hemes. Our results describe the effect of the subtle protein-induced changes on the nonplanarity of the HbA hemes that may play a role in the regulation of their oxygen affinity.