Manchester Interdisciplinary Biocentre, Faculty of Life Sciences, University of Manchester, Manchester, UK.
FEBS J. 2012 May;279(9):1534-44. doi: 10.1111/j.1742-4658.2011.08442.x. Epub 2012 Jan 9.
There is a mounting body of evidence to suggest that enzyme motions are linked to function, although the design of informative experiments aiming to evaluate how this motion facilitates reaction chemistry is challenging. For the family of diflavin reductase enzymes, typified by cytochrome P450 reductase, accumulating evidence suggests that electron transfer is somehow coupled to large-scale conformational change and that protein motions gate the electron transfer chemistry. These ideas have emerged from a variety of experimental approaches, including structural biology methods (i.e. X-ray crystallography, electron paramagnetic/NMR spectroscopies and solution X-ray scattering) and advanced spectroscopic techniques that have employed the use of variable pressure kinetic methodologies, together with solvent perturbation studies (i.e. ionic strength, deuteration and viscosity). Here, we offer a personal perspective on the importance of motions to electron transfer in the cytochrome P450 reductase family of enzymes, drawing on the detailed insight that can be obtained by combining these multiple structural and biophysical approaches.
越来越多的证据表明，酶的运动与功能有关，尽管设计有意义的实验来评估这种运动如何促进反应化学是具有挑战性的。对于双黄素还原酶家族的酶，以细胞色素 P450 还原酶为典型代表，越来越多的证据表明，电子转移与大规模构象变化有关，并且蛋白质运动控制着电子转移化学。这些想法来自于各种实验方法，包括结构生物学方法（即 X 射线晶体学、电子顺磁共振/NMR 光谱学和溶液 X 射线散射）和先进的光谱技术，这些技术采用了可变压力动力学方法，以及溶剂扰动研究（即离子强度、氘化和粘度）。在这里，我们结合这些多种结构和生物物理方法获得的详细见解，从个人的角度探讨了运动对细胞色素 P450 还原酶家族酶中电子转移的重要性。
