Mazmanian Karine, Sargsyan Karen, Lim Carmay
Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
Department of Chemistry, National Tsing Hua University, Hsinchu 300, Taiwan.
J Am Chem Soc. 2020 Jun 3;142(22):9861-9871. doi: 10.1021/jacs.0c02430. Epub 2020 May 19.
Proteins form complex biological machineries whose functions in the cell are highly regulated at both the cellular and molecular levels. Cellular regulation of protein functions involves differential gene expressions, post-translation modifications, and signaling cascades. Molecular regulation, on the other hand, involves tuning an optimal local protein environment for the functional site. Precisely how a protein achieves such an optimal environment around a given functional site is not well understood. Herein, by surveying the literature, we first summarize the various reported strategies used by certain proteins to ensure their correct functioning. We then formulate three key physicochemical factors for regulating a protein's functional site, namely, (i) its immediate interactions, (ii) its solvent accessibility, and (iii) its conformational flexibility. We illustrate how these factors are applied to regulate the functions of free/metal-bound Cys and Zn sites in proteins.
蛋白质构成复杂的生物机器，其在细胞中的功能在细胞和分子水平上都受到高度调控。蛋白质功能的细胞调控涉及差异基因表达、翻译后修饰和信号级联反应。另一方面，分子调控涉及为功能位点调整最佳的局部蛋白质环境。目前尚不清楚蛋白质究竟是如何在给定的功能位点周围实现这样一个最佳环境的。在此，通过查阅文献，我们首先总结了某些蛋白质为确保其正确功能而采用的各种已报道策略。然后，我们提出了调控蛋白质功能位点的三个关键物理化学因素，即：(i) 其直接相互作用，(ii) 其溶剂可及性，以及 (iii) 其构象灵活性。我们举例说明了这些因素如何应用于调控蛋白质中游离/金属结合的半胱氨酸和锌位点的功能。
