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.

氨酰基-tRNA 合成酶对于蛋白质合成过程中氨基酸和 tRNA 的正确配对至关重要 合成。大多数氨酰基-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，它是某些细菌中的 I 类酶， 古细菌，但在其他方面都是 I1 类的成员。 I 类赖氨酰-tRNA 合成酶存在于许多 与人类 II 类酶根本不同，识别 I 类酶 细菌酶作为开发抗感染药物的潜在目标。 该提案的目的是研究最近发现的 I 类物质中的结构/功能关系 类型赖氨酰-tRNA 合成酶。主要目标包括： i) 确定 I 类和 II 类赖氨酰-tRNA 合成酶如何识别和区分赖氨酸 和赖氨酸类似物。 ii) 鉴定决定赖氨酸 tRNA 体外和体内识别的蛋白质-RNA 相互作用。 这些实验的结果将揭示相同的活性（赖氨酸与赖氨酸 tRNA 的连接）如何能够 可以在两个完全不同的结构框架内实现。反过来，这将为 开发专门针对 I 类赖氨酰-tRNA 合成酶的疗法。