Dissecting Catalytic Features of Diverse Methionyl-tRNA Synthetase Enzymes

蛋白质合成是任何生物体最重要的细胞活动之一。 氨酰-tRNA合成酶是蛋白质生物合成中必需的酶，催化氨基酸与tRNA衔接子的连接，用于核糖体解码遗传信息。 许多tRNA合成酶在细胞调节中具有与其翻译功能分开的额外作用。 本项目研究了甲硫氨酰-tRNA合成酶的机制特征，甲硫氨酰-tRNA合成酶是一种独特的tRNA合成酶，其tRNA异源受体在翻译起始与延伸中具有不同的命运。tRNA合成酶在不同的生物体中以单体和二聚体形式存在，并且在某些生物体中，它们含有附加的蛋白质结构域，以扩展其细胞功能。 利用分子生物学，计算化学和机械酶学的工具，这项研究旨在扩大蛋白质生物合成和新的细胞活动中进化上不同的甲硫氨酰-tRNA合成酶的理解。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培训。当地社区通过课后科学俱乐部为有风险的中学生提供动手丰富活动而受到影响。 这些科学俱乐部由本科生领导，参加关于妇女参与科学的历史的研讨会课程，从而提供了一个现实世界的例子，说明增加在科学领域代表性通常不足的人口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.