Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, Via Cintia, I-80126, Napoli, Italy.
Metallomics. 2017 Nov 15;9(11):1534-1547. doi: 10.1039/c7mt00219j.
The characterization of the interactions between biological macromolecules (proteins and nucleic acids) and metal-based drugs is a fundamental prerequisite for understanding their mechanisms of action. X-ray crystallography enables the structural analysis of such complexes with atomic level detail. However, this approach requires the preparation of highly diffracting single crystals, the measurement of diffraction patterns and the structural analysis and interpretation of macromolecule-metal interactions from electron density maps. In this review, we describe principles and methods used to grow and optimize crystals of protein-metallodrug adducts, to determine metal binding sites and to assign and validate metal ligands. Examples from the literature and experience in our own laboratory are provided and key challenges are described, notably crystallization and molecular model refinement against the X-ray diffraction data.
生物大分子（蛋白质和核酸）与金属基药物相互作用的特征描述是理解它们作用机制的基本前提。X 射线晶体学能够以原子级的细节分析此类复合物的结构。然而，这种方法需要制备高度衍射的单晶、测量衍射图谱以及从电子密度图中分析和解释大分子-金属相互作用。在这篇综述中，我们描述了用于生长和优化蛋白-金属药物加合物晶体、确定金属结合位点以及分配和验证金属配体的原理和方法。提供了文献中的例子和我们自己实验室的经验，并描述了关键挑战，特别是针对 X 射线衍射数据的结晶和分子模型细化。
