Global Analysis of Heme Proteins Elucidates the Correlation between Heme Distortion and the Heme-Binding Pocket
Global Analysis of Heme Proteins Elucidates the Correlation between Heme Distortion and the Heme-Binding Pocket
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DOI：
10.1021/acs.jcim.1c01315
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发表时间：
2022-02-28
影响因子：
5.6
通讯作者：
Takano, Yu
中科院分区：
文献类型：
--
作者：
Kondo, Hiroko X.;Fujii, Masanori;Takano, Yu
血红素蛋白从电子转移和化学催化到氧运输和/或储存起着多种多样的重要生物学作用。尽管血红素卟啉的失真与血红素的物理特性（例如氧化还原电位和氧亲和力）相关，但血红素失真与血红素蛋白环境之间的关系尚不清楚。她;我们检验了以下假设：血红素结合口袋的蛋白质环境决定血红素失真（构象）。我们使用机器学习分析了血红素结合口袋的氨基酸组成与沿12个振动模式的血红素失真的大小之间的相关性。在三种最低的振动模式中检测到相关性。在几乎相同的血红素结合口袋中的血红素扭曲的分析支持了这一概念。我们的分析表明，血红素结合的口袋环境是影响血红素卟啉沿最低三种最低振动模式的变形的主要因素。此外，对血红素卟啉失真的统计分析表明，荷叶褶皱和呼吸失真的分布峰从0（平衡结构）转移。皱纹和呼吸畸变都与血红素的氧化还原电位相关，因此与平面分子相比，具有这些畸变的血红素分子具有低的氧化还原电位。这些发现解释了血红素的结构功能关系。
Heme proteins play diverse and important biological roles, from electron transfer and chemical catalysis to oxygen transport and/or storage. Although the distortion of heme porphyrin correlates with the physical properties of heme, such as the redox potential and oxygen affinity, the relationship between heme distortion and the heme protein environment is unclear. Her; we tested the hypothesis that the protein environment of the heme-binding pocket determines heme distortion (conformation). We analyzed the correlations between the amino acid composition of the heme-binding pocket and the magnitude of heme distortion along 12 vibrational modes using machine learning. A correlation was detected in the three lowest vibrational modes. Analysis of heme distortions in nearly the same environments of the heme-binding pocket supported this notion. Our analyses indicate that the heme-binding pocket environment is a major factor impacting the distortion of heme porphyrin along the three lowest vibrational modes. In addition, statistical analysis of the distortion of heme porphyrin revealed that the peaks of distributions of the ruffling and breathing distortions are shifted from 0 (the equilibrium structure). Both the ruffling and breathing distortions are correlated with the redox potential of heme, so that heme molecules with these distortions have a lower redox potential than planar molecules. These findings explain the structure-function relationship of heme.