Kondo Hiroko X, Takano Yu
Faculty of Engineering, Kitami Institute of Technology, School of Regional Innovation and Social Design Engineering, 165 Koen-cho, Kitami 090-8507, Japan.
Graduate School of Information Sciences, Hiroshima City University, 3-4-1 Ozukahigashi Asaminamiku, Hiroshima 731-3194, Japan.
Life (Basel). 2022 Jan 29;12(2):210. doi: 10.3390/life12020210.
Heme is located in the active site of proteins and has diverse and important biological functions, such as electron transfer and oxygen transport and/or storage. The distortion of heme porphyrin is considered an important factor for the diverse functions of heme because it correlates with the physical properties of heme, such as oxygen affinity and redox potential. Therefore, clarification of the relationship between heme distortion and the protein environment is crucial in protein science. Here, we analyzed the fluctuation in heme distortion in the protein environment for hemoglobin and myoglobin using molecular dynamics (MD) simulations and quantum mechanical (QM) calculations as well as statistical analysis of the protein structures of hemoglobin and myoglobin stored in Protein Data Bank. Our computation and statistical analysis showed that the protein environment for hemoglobin and myoglobin prominently affects the doming distortion of heme porphyrin, which correlates with its oxygen affinity, and that the magnitude of distortion is different between hemoglobin and myoglobin. These results suggest that heme distortion is affected by its protein environment and fluctuates around its fitted conformation, leading to physical properties that are appropriate for protein functions.
血红素位于蛋白质的活性位点，具有多种重要的生物学功能，如电子传递、氧气运输和/或储存。血红素卟啉的畸变被认为是血红素具有多种功能的重要因素，因为它与血红素的物理性质相关，如氧亲和力和氧化还原电位。因此，阐明血红素畸变与蛋白质环境之间的关系在蛋白质科学中至关重要。在这里，我们使用分子动力学（MD）模拟和量子力学（QM）计算以及对存储在蛋白质数据库中的血红蛋白和肌红蛋白的蛋白质结构进行统计分析，来分析蛋白质环境中血红蛋白和肌红蛋白的血红素畸变波动情况。我们的计算和统计分析表明，血红蛋白和肌红蛋白的蛋白质环境显著影响血红素卟啉的穹顶畸变，这与其氧亲和力相关，并且血红蛋白和肌红蛋白之间的畸变程度不同。这些结果表明，血红素畸变受其蛋白质环境影响，并围绕其拟合构象波动，从而产生适合蛋白质功能的物理性质。
