Institute of Biomedical Sciences, Academia Sinica , Taipei 11529 , Taiwan.
Chemical Biology and Molecular Biophysics Program , Taiwan International Graduate Program, Academia Sinica , Taipei 10617 , Taiwan.
Inorg Chem. 2018 Nov 19;57(22):14052-14061. doi: 10.1021/acs.inorgchem.8b01029. Epub 2018 Jun 15.
Hydrogen bonds to metal-ligands in proteins play a vital role in biological function. They help to stabilize/protect the metal complex and enhance metal-binding affinity/specificity, enzyme-substrate recognition, and enzyme activation. Yet, knowledge of the preferred hydrogen-bonding partners of metal ligands in different metalloproteins is lacking. Using well-calibrated methods, we have determined the preferred hydrogen-bonding partners of Cys bound to native Zn or xenobiotic Cd in Zn-fingers of varying net charge and solvent accessibility as well as the key factors underlying the observed preference. We show how secondary hydrogen-bonding interactions with metal-bound thiolates might exert a significant impact on Zn→Cd substitution and thus protein function. Knowing which Zn-fingers may be vulnerable to structural deformation by Cd is important since this would lead to their inactivation, which might impair cell growth, differentiation, cell-cycle control, and DNA repair.
氢键在蛋白质中的金属配体中起着至关重要的作用，对生物功能有重要影响。它们有助于稳定/保护金属配合物，并提高金属结合亲和力/特异性、酶-底物识别和酶激活。然而，对于不同金属蛋白中金属配体的首选氢键供体的知识仍然缺乏。我们使用经过良好校准的方法，确定了带正电荷和溶剂可及性不同的锌指中 Cys 与天然 Zn 或外源 Cd 结合时的首选氢键供体，以及观察到的偏好的基础关键因素。我们展示了与金属结合的硫醇的次级氢键相互作用如何对 Zn→Cd 取代产生重大影响，从而影响蛋白质功能。了解哪些锌指可能容易受到 Cd 的结构变形影响很重要，因为这会导致它们失活，从而可能损害细胞生长、分化、细胞周期控制和 DNA 修复。
