Biochemistry of Class I lysyl-tRNA synthetases

I 类赖氨酰-tRNA 合成酶的生物化学

• 批准号: 7169592
• 负责人: MICHAEL IBBA
• 金额: $ 24.61万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7169592
• 关键词: Active Sites; Amino Acids; Amino Acyl-tRNA Synthetases; Anti-Infective Agents; Anticodon; Archaea; Bacteria; Binding; Biochemistry; Borrelia burgdorferi; Charge; Class; Complex; Discrimination; Enzymes; Escherichia; Goals; Human; In Vitro; Lysine; Lysine-Specific tRNA; Lysine-tRNA Ligase; Molecular; Nucleotides; Numbers; Pattern Recognition; Phylogenetic Analysis; Phylogeny; Protein Biosynthesis; Proteins; RNA-Protein Interaction; Research Personnel; Role; Site; Specificity; Structure; Structure-Activity Relationship; Testing; Therapeutic; Transfer RNA; Variant; base; in vivo; inhibitor/antagonist; lysin; lysine analog; lysine-tRNA; member; mutant; pathogenic bacteria; programs; research study

Aminoacyl-tRNA synthetases are essential for the correct pairing of amino acids and tRNAs during protein synthesis. Most aminoacyl-tRNA synthetases belong to one of two unrelated structural classes. The only widespread exceptions are the lysyl-tRNA synthetases, which are class I enzymes in certain bacteria and archaea but are otherwise members of class I1. The class I lysyl-tRNA synthetase is found in a number of pathogenic bacteria and is fundamentally different from the human class II enzyme, identifying the class I bacterial enzyme as a potential target for developing anti-infective agents. The aim of this proposal is to investigate structure/function relationships in the recently discovered class I- type lysyl-tRNA synthetases. The major goals include: i) Determining how class I and class II lysyl-tRNA synthetases recognize and discriminate between lysine and lysine analogues. ii) Identifying the protein-RNA interactions that determine lysine tRNA recognition in vitro and in vivo. The results of these experiments will reveal how the same activity (attachment of lysine to lysine tRNA) can be achieved within two completely different structural frameworks. This, in turn, will provide a framework for developing therapeutics specifically targeted against the class I lysyl-tRNA synthetase.

氨酰-tRNA合成酶是蛋白质过程中氨基酸和tRNA正确配对所必需的 综合。大多数氨酰-tRNA合成酶属于两个不相关的结构类别之一。唯一的 普遍的例外是赖氨酰-tRNA合成酶，它是某些细菌和 古生菌，但在其他方面是纲I1的成员。I类赖氨酰-tRNA合成酶存在于许多 致病菌，与人类第II类酶根本不同，识别第I类 细菌酶作为开发抗感染药物的潜在靶点。 这个建议的目的是研究最近发现的I类的结构/功能关系- 键入赖氨酰-tRNA合成酶。主要目标包括： I)确定第I类和第II类赖氨酸-tRNA合成酶如何识别和区分赖氨酸 和赖氨酸类似物。 Ii)确定在体外和体内决定赖氨酸tRNA识别的蛋白质-RNA相互作用。 这些实验的结果将揭示同样的活动(赖氨酸与赖氨酸tRNA的连接)如何 在两个完全不同的结构框架内实现。这反过来将提供一个框架，用于 开发专门针对I类赖氨酰-tRNA合成酶的疗法。