Department of Molecular Enzymology, Göttingen Center of Molecular Biosciences, Georg-August University Göttingen, Julia-Lermontowa-Weg 3, D-37077 Göttingen, Germany; Max-Planck-Institute for Multidisciplinary Sciences, Am Fassberg 11, D-37077 Göttingen, Germany.
Curr Opin Struct Biol. 2022 Oct;76:102441. doi: 10.1016/j.sbi.2022.102441. Epub 2022 Aug 18.
Enzymes that use thiamin diphosphate (ThDP), the biologically active derivative of vitamin B1, as a cofactor play important roles in cellular metabolism in all domains of life. The analysis of ThDP enzymes in the past decades have provided a general framework for our understanding of enzyme catalysis of this protein family. In this review, we will discuss recent advances in the field that include the observation of "unusual" reactions and reaction intermediates that highlight the chemical versatility of the thiamin cofactor. Further topics cover the structural basis of cooperativity of ThDP enzymes, novel insights into the mechanism and structure of selected enzymes, and the discovery of "superassemblies" as reported, for example, acetohydroxy acid synthase. Finally, we summarize recent findings in the structural organisation and mode of action of 2-keto acid dehydrogenase multienzyme complexes and discuss future directions of this exciting research field.
使用硫胺素二磷酸（ThDP）作为辅因子的酶在所有生命领域的细胞代谢中都发挥着重要作用，而 ThDP 是维生素 B1 的生物活性衍生物。过去几十年来对 ThDP 酶的分析为我们理解该蛋白家族的酶催化提供了一个通用框架。在这篇综述中，我们将讨论该领域的最新进展，包括对“不寻常”反应和反应中间体的观察，这些观察突出了硫胺素辅因子的化学多功能性。进一步的主题包括 ThDP 酶协同作用的结构基础、对选定酶的机制和结构的新见解，以及“超组装体”的发现，例如乙酰羟酸合酶。最后，我们总结了 2-酮酸脱氢酶多酶复合物的结构组织和作用模式的最新发现，并讨论了这一令人兴奋的研究领域的未来方向。
