Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, Via Cintia, I-80126, Napoli, Italy.
Chem Commun (Camb). 2021 Feb 11;57(11):1295-1307. doi: 10.1039/d0cc08053e.
Protein metalation is a process that determines the formation of adducts upon reaction of metal compounds with proteins. Protein metalation plays a crucial role in different fields, determining the mechanism of action and toxicity of metal-based drugs and the basis for the rational design of artificial metalloenzymes and protein-based metallodrug-delivery systems. Recent advances in structural studies unveiling the basis of the metal compounds/protein recognition process are briefly discussed here. The analysis of the structures of Pt, Au, Ru, Re, Pd, Ir, Os, Rh and Pt-As/protein adducts reveals that metal compounds (i) can bind proteins via non-covalent interactions or via coordination to selected residue side chains upon the release of labile ligands; (ii) can undergo reduction/oxidation processes upon protein binding that in turn can lead to changes in the metal coordination sphere and breakdown of the metal compound; (iii) can bind different protein recognition sites with a preference for selected side chains that is governed by hard and soft acids and bases, and with the number and type of binding sites changing over time; and (iv) can retain a certain degree of flexibility and reactivity in the final metal/protein adduct.
蛋白质的金属化作用是一个决定金属化合物与蛋白质反应时形成加合物的过程。蛋白质的金属化作用在不同领域中起着至关重要的作用，决定了基于金属的药物的作用机制和毒性，以及人工金属酶和基于蛋白质的金属药物传递系统的合理设计的基础。本文简要讨论了揭示金属化合物/蛋白质识别过程基础的结构研究的最新进展。对 Pt、Au、Ru、Re、Pd、Ir、Os、Rh 和 Pt-As/蛋白质加合物结构的分析表明，金属化合物 (i) 可以通过非共价相互作用或通过与选定的侧链配位结合蛋白质，在释放不稳定配体后；(ii) 可以在蛋白质结合时经历还原/氧化过程，这反过来又会导致金属配位球的变化和金属化合物的分解；(iii) 可以与不同的蛋白质识别位点结合，对选定的侧链具有偏好性，这由硬酸和软酸的原则决定，并且结合位点的数量和类型随时间而变化；以及 (iv) 在最终的金属/蛋白质加合物中可以保持一定程度的灵活性和反应性。
