Meisburger Steve P, Thomas William C, Watkins Maxwell B, Ando Nozomi
Department of Chemistry, Princeton University , Princeton, New Jersey 08544, United States.
Chem Rev. 2017 Jun 28;117(12):7615-7672. doi: 10.1021/acs.chemrev.6b00790. Epub 2017 May 30.
X-ray scattering is uniquely suited to the study of disordered systems and thus has the potential to provide insight into dynamic processes where diffraction methods fail. In particular, while X-ray crystallography has been a staple of structural biology for more than half a century and will continue to remain so, a major limitation of this technique has been the lack of dynamic information. Solution X-ray scattering has become an invaluable tool in structural and mechanistic studies of biological macromolecules where large conformational changes are involved. Such systems include allosteric enzymes that play key roles in directing metabolic fluxes of biochemical pathways, as well as large, assembly-line type enzymes that synthesize secondary metabolites with pharmaceutical applications. Furthermore, crystallography has the potential to provide information on protein dynamics via the diffuse scattering patterns that are overlaid with Bragg diffraction. Historically, these patterns have been very difficult to interpret, but recent advances in X-ray detection have led to a renewed interest in diffuse scattering analysis as a way to probe correlated motions. Here, we will review X-ray scattering theory and highlight recent advances in scattering-based investigations of protein solutions and crystals, with a particular focus on complex enzymes.
X射线散射特别适合用于研究无序系统，因此有潜力深入了解衍射方法无法适用的动态过程。特别是，虽然X射线晶体学在半个多世纪以来一直是结构生物学的主要手段，并将继续保持这一地位，但该技术的一个主要局限性是缺乏动态信息。溶液X射线散射已成为研究涉及大的构象变化的生物大分子的结构和作用机制的宝贵工具。这类系统包括在指导生化途径的代谢通量中起关键作用的变构酶，以及合成具有药物应用的次级代谢产物的大型装配线型酶。此外，晶体学有潜力通过与布拉格衍射叠加的漫散射图案提供有关蛋白质动力学的信息。从历史上看，这些图案很难解释，但X射线检测的最新进展重新激发了人们对漫散射分析的兴趣，将其作为探测相关运动的一种方法。在这里，我们将回顾X射线散射理论，并重点介绍基于散射的蛋白质溶液和晶体研究的最新进展，特别关注复合酶。
