Ramadas N, Rifkind J M
Laboratory of Cellular and Molecular Biology, Molecular Dynamics Section, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
Biophys J. 1999 Apr;76(4):1796-811. doi: 10.1016/S0006-3495(99)77340-6.
Spectroscopic studies indicate an interaction of the distal histidine with the heme iron as well as the transmission of distal heme perturbations across the alpha1beta1 interface. Molecular dynamics simulations have been used to explain the molecular basis for these processes. Using a human methemoglobin alpha beta dimer, it has been shown that at 235 K after 61 ps, a rearrangement occurs in the alpha-chain corresponding to the formation of a bond with the distal histidine. This transition does not take place in the beta-chain during a 100-ps simulation and is reversed at 300 K. The absence of the distal histidine transition in the isolated chains and with the interface frozen indicate the involvement of the alphabeta interface. A detailed analysis of the simulation has been performed in terms of RMS fluctuations, domain cross-correlation maps, the disruption of helix hydrogen bonds, as well changes in electrostatic interactions and dihedral angles. This analysis shows that the rearrangements in the alpha-chain necessary to bring the histidine closer to the iron involve alterations primarily in the CD loop and at the interface. Communication to the beta-chain distal pocket is propagated by increased interactions of the alpha-chain B helix with the beta-chain G-GH-H segment and the flexibility in the EF loop. The G helices shown to be involved in propagation of perturbation across the alpha1beta1 interface extend into the alpha1beta2 interfaces, providing a mechansim whereby distal interactions can modulate the T<==>R transition in hemoglobin.
光谱研究表明，远端组氨酸与血红素铁之间存在相互作用，并且远端血红素扰动可通过α1β1界面进行传递。分子动力学模拟已被用于解释这些过程的分子基础。利用人高铁血红蛋白αβ二聚体，研究表明，在235K温度下经过61皮秒后，α链中会发生重排，这与远端组氨酸形成化学键相对应。在100皮秒的模拟过程中，β链并未发生这种转变，且在300K时这种转变会逆转。在分离的链中以及界面冻结的情况下，远端组氨酸未发生转变，这表明αβ界面参与其中。已根据均方根波动、结构域互相关图谱、螺旋氢键的破坏以及静电相互作用和二面角的变化对模拟进行了详细分析。该分析表明，使组氨酸更靠近铁所需的α链重排主要涉及CD环和界面处的改变。α链B螺旋与β链G - GH - H片段之间相互作用的增加以及EF环的灵活性促进了与β链远端口袋的通信。已表明参与扰动通过α1β1界面进行传递的G螺旋延伸至α1β2界面，从而提供了一种机制，通过该机制远端相互作用可调节血红蛋白中的T⇔R转变。
