Dissecting Catalytic Features of Diverse Methionyl-tRNA Synthetase Enzymes

蛋白质合成是任何生物体最关键的细胞活动之一。氨基酰基-tRNA合成酶是蛋白质生物合成中的重要酶，催化氨基酸与tRNA接头连接，对遗传信息进行核糖体解码。许多tRNA合成酶除了在翻译中发挥作用外，还在细胞调节中发挥着额外的作用。本项目研究了甲硫酰-tRNA合成酶的机制特征，这是一种独特的tRNA合成酶，因为它的tRNA异构体在翻译起始和延伸方面有不同的命运。TRNA合成酶在不同的生物体中以单体和二聚体的形式存在，在一些生物体中，它们含有附加的蛋白结构域，扩展了它们的细胞功能。利用分子生物学、计算化学和机械酶学的工具，本研究试图扩大对进化上不同的蛋氨酰-tRNA合成酶在蛋白质生物合成和新的细胞活动中的理解。更广泛的影响。该项目为文科大学维克森林大学的新兴科学家提供现代生物化学技术方面的培训。当地社区受到课外科学俱乐部的影响，这些俱乐部为有风险的中学生提供实践丰富活动。这些科学俱乐部是由本科生在一门关于女性科学史的研讨会课程中领导的，从而提供了一个现实世界的例子，说明了增加通常在科学领域代表性较低的人群的参与所固有的挑战。

Protein synthesis is one of the most critical cellular activities of any organism. Aminoacyl-tRNA synthetases are essential enzymes in protein biosynthesis, catalyzing the attachment of amino acids to tRNA adaptors for ribosomal decoding of genetic information. Many tRNA synthetases have additional roles in cellular regulation separate from their function in translation. This project investigates mechanistic features of methionyl-tRNA synthetase, which is a distinctive tRNA synthetase in that its tRNA isoacceptors have divergent fates in translational initiation versus elongation. The tRNA synthetases exist in both monomeric and dimeric forms in different organisms, and, in some organisms, they contain appended protein domains that expand their cellular functions. Using tools of molecular biology, computational chemistry, and mechanistic enzymology, this research seeks to expand understanding of evolutionarily distinct methionyl-tRNA synthetase enzymes in protein biosynthesis and novel cellular activities. Broader Impacts. The project provides training in modern biological chemistry techniques to emerging scientists at Wake Forest University, a liberal arts university. The local community is impacted through after-school science clubs offering hands-on enrichment activities for at-risk middle school students. These science clubs are led by undergraduate students in a seminar course on the history of women in science, thus providing a real-world example of the challenges inherent in increasing participation of populations typically underrepresented in science.