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.

氨基酰基-TRNA合成酶对于蛋白质中氨基酸和TRNA的正确配对至关重要 合成。大多数氨基酰基-TRNA合成酶属于两个无关的结构类别之一。唯一的 广泛的例外是赖氨基-TRNA合成酶，它们是某些细菌中的I类酶 古细菌，但否则是I1级的成员。在许多人中发现了I类赖氨酸-TRNA合成酶 致病细菌，从根本上与人类II类酶不同，鉴定了I类 细菌酶是发展抗感染剂的潜在靶标。 该建议的目的是研究最近发现的I类中的结构/功能关系 型晶体基-TRNA合成酶。主要目标包括： i）确定I类和II类赖氨酸-TRNA合成酶如何识别并区分赖氨酸 和赖氨酸类似物。 ii）确定在体外和体内确定赖氨酸tRNA识别的蛋白-RNA相互作用。 这些实验的结果将揭示相同的活性（赖氨酸附着在赖氨酸tRNA上）如何 可以在两个完全不同的结构框架内实现。反过来，这将为 开发针对I类赖氨酸-TRNA合成酶的治疗剂。