Singh Sarkkarai Raja, Prakash Subash, Vasu Veerapandy, Karunakaran Chandran
Biomedical Research Laboratory, Department of Physics, VHNSN College, Virudhunagar 626 001, India.
J Mol Graph Model. 2009 Oct;28(3):270-7. doi: 10.1016/j.jmgm.2009.08.005. Epub 2009 Aug 8.
Cytochrome c (cyt c), a mitochondrial protein, has dual functions in controlling both cellular energetic metabolism and apoptosis (programmed cell death). During apoptosis, cyt c (Fe(3+)) released into the cytosol initiates caspase activation leading to apoptosis. Since, X-ray crystallography gives only the static structure, we report here the dynamic behavior of holo and apo wild type (WT), Y67F and F82H mutant cyt c's (Fe(3+)) in their apoptotic states. Four nanosecond MD simulations were run for holo WT, Y67F and F82H cyt c's with and without Fe...S (Met-80) bond and also for apo WT and mutated cyt c's (Y67F and F82H) in water using GROMOS96 force field. Mutations of Y67F and F82H resulted in the decrease of backbone and Calpha RMSDs, and radii of gyration (backbone and protein) in both the holo and apo forms. MD and ED results revealed that the flexibility of mutated holo cyt c's decreased perhaps affecting their ability to take part in mitochondrial electron/proton transfer process. Without Fe...S bond, the backbone and Calpha RMSD increased in holo cyt c's perhaps resulting in enhanced peroxidase activity. ED revealed that four to six eigenvectors involved in over all motions of holo cyt c's without Fe...S bond, and six to eight eigenvectors in apo cyt c's in comparison to three to four eigenvectors for holo cyt c's with Fe...S bond.
细胞色素c（cyt c）是一种线粒体蛋白，在控制细胞能量代谢和凋亡（程序性细胞死亡）方面具有双重功能。在凋亡过程中，释放到细胞质中的细胞色素c（Fe(3+)）启动半胱天冬酶激活，导致细胞凋亡。由于X射线晶体学仅给出静态结构，我们在此报告全酶型和脱辅基型野生型（WT）、Y67F和F82H突变体细胞色素c（Fe(3+)）在其凋亡状态下的动态行为。使用GROMOS96力场对全酶型WT、Y67F和F82H细胞色素c进行了四次纳秒级分子动力学（MD）模拟，模拟有和没有Fe...S（Met-80）键的情况，同时也对脱辅基型WT和突变型细胞色素c（Y67F和F82H）在水中进行了模拟。Y67F和F82H突变导致全酶型和脱辅基型的主链和α碳原子的均方根偏差（RMSDs）以及回转半径（主链和蛋白质）减小。分子动力学和弹性网络动力学（ED）结果表明，突变的全酶型细胞色素c的灵活性降低，这可能影响它们参与线粒体电子/质子转移过程的能力。没有Fe...S键时，全酶型细胞色素c的主链和α碳原子的RMSD增加，这可能导致过氧化物酶活性增强。弹性网络动力学显示，没有Fe...S键的全酶型细胞色素c的整体运动涉及四到六个本征向量，脱辅基型细胞色素c涉及六到八个本征向量，而有Fe...S键的全酶型细胞色素c涉及三到四个本征向量。
