Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA.
Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA.
Curr Opin Chem Biol. 2022 Apr;67:102110. doi: 10.1016/j.cbpa.2021.102110. Epub 2022 Jan 31.
There are ten nickel enzymes found across biological systems, each with a distinct active site and reactivity that spans reductive, oxidative, and redox-neutral processes. We focus on the reductive enzymes, which catalyze reactions that are highly germane to the modern-day climate crisis: [NiFe] hydrogenase, carbon monoxide dehydrogenase, acetyl coenzyme A synthase, and methyl coenzyme M reductase. The current mechanistic understanding of each enzyme system is reviewed along with existing knowledge gaps, which are addressed through the development of protein-derived models, as described here. This opinion is intended to highlight the advantages of using robust protein scaffolds for modeling multiscale contributions to reactivity and inspire the development of novel artificial metalloenzymes for other small molecule transformations.
生物系统中发现了十种镍酶，每种酶都具有独特的活性位点和反应性，涵盖了还原、氧化和氧化还原中性过程。我们专注于还原酶，它们催化与现代气候危机高度相关的反应：[NiFe]氢化酶、一氧化碳脱氢酶、乙酰辅酶 A 合酶和甲基辅酶 M 还原酶。本文回顾了每个酶系统的当前机械理解以及现有知识空白，并通过开发蛋白质衍生模型来解决这些问题。本文旨在强调使用稳健的蛋白质支架来模拟反应性的多尺度贡献的优势，并激发为其他小分子转化开发新型人工金属酶的发展。
