Modeling of ligation-induced helix/loop displacements in myoglobin: Toward an understanding of hemoglobin allostery
Modeling of ligation-induced helix/loop displacements in myoglobin: Toward an understanding of hemoglobin allostery
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DOI：
10.1021/ja057318h
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发表时间：
2006-04-26
影响因子：
15
通讯作者：
Spiro, TG
中科院分区：
文献类型：
--
作者：
Guallar, V;Jarzecki, AA;Spiro, TG
结合量子和分子力学（QM/MM）方法和蛋白质结构预测算法，计算了CO从肌红蛋白（Mb）解离的螺旋和环运动。利用序列位移图将结果与高分辨率晶体学数据进行了比较。这些图提供了一种评价主链节段运动的无偏方法；它们解决了MbCO和脱氧ymb两组高分辨率晶体结构之间的明显分歧。CO离子的QM/MM模型再现了实验观察到的自旋态和光解晶体结构。CO解离的主要作用是E和F螺旋的一致旋转，它们将血红素像翻盖一样固定住。旋转是对委托力的反应，由于Fe自旋转换，促使F螺旋远离血红素，并允许E螺旋向血红素坍塌，因为远端非键接触被解除。额外的螺旋和环形位移源于这些主要事件。特别是，CD环被发现是由于与水分子的空间相互作用而重新定位的，水分子在脱氧中与远端组氨酸形成h键。类似的EF旋转和CID环位移被认为是血红蛋白从R状态到T状态变构途径的第一步。
Combining quantum and molecular mechanics (QM/MM) methods and protein structure prediction algorithms, helix and loop movements are computed along the pathway of CO dissociation from myoglobin (Mb). The results are compared with high-resolution crystallographic data using sequence-displacement graphs. These graphs provide an unbiased method for evaluating main-chain segmental motions; they resolve an apparent disagreement between two sets of high-resolution crystal structures for MbCO and deoxyMb. The QM/MM modeling of the CO deligation reproduces the experimentally observed spin states and photodissociated crystal structure. The principal effect of CO dissociation is shown to be a concerted rotation of the E and F helices, which hold the heme like a clamshell. The rotation is a response to deligation forces, which impel the F helix away from the heme because of the Fe spin conversion, and which allow the E helix to collapse toward the heme as nonbonded contacts on the distal side are relieved. Additional helix and loop displacements stem from these primary events. In particular, the CD loop is found to be repositioned as a result of steric interactions with the water molecule that becomes H-bonded to the distal histidine in deoxyMb. A similar EF rotation and CID loop displacement are proposed to be the first steps along the allosteric pathway from the R to the T state in hemoglobin.