在结构指导下发现了能调节tRNA功能的代谢物carboxy-SAM
Jungwook Kim1, Hui Xiao, Jeffrey B Bonanno
1Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA. jungwook.kim@einstein.yu.edu
Nature
|May 17, 2013
概括
研究人员发现了一种新代谢物,carboxy-S-adenosyl-l-methionine (Cx-SAM),以及它在转移RNA修饰中的作用. 这一发现揭示了SAM-依赖的甲基转移酶超级家族中的新功能.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 代谢学 代谢学 代谢学
背景情况:
- 在生物学中,识别新代谢物及其功能至关重要.
- 射线晶体学可以发现意想不到的蛋白质-连接体相互作用.
- 这些相互作用为新的生物活动和监管机制提供了洞察力.
研究的目的:
- 为了识别和描述一种新型代谢物,碳氧-S-腺-l-氨酸 (Cx-SAM).
- 阐明Cx-SAM的生物合成途径和生物功能.
- 探索Cx-SAM在转移RNA修饰中的作用.
主要方法:
- 用X射线晶体学来确定CmoA的结构,并与Cx-SAM复合.
- 机械分析以了解SAM的酶转化为Cx-SAM.
- 生物化学试验研究CmoB在tRNA修饰中的功能.
主要成果:
- 发现了carboxy-S-adenosyl-l-methionine (Cx-SAM) 和其生物合成途径,其中涉及CmoA.
- 在Cx-SAM合成中,鉴定了前酸作为碳基捐赠物和独特的化物中间体.
- 描述CmoB作为一个碳素甲基转移酶,它通过Cx-SAM修改tRNA,扩大了编码子识别.
结论:
- CmoA和CmoB是第一个被确定为Cx-SAM的合成酶和转移酶.
- 这些发现扩大了SAM-依赖的甲基转移酶超级家族的已知功能.
- 这项研究强调了结构基因组学在发现新代谢物及其生物作用方面的实用性.
相关概念视频
Transfer RNA Synthesis
One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
tRNA Activation
Aminoacyl-tRNA synthetases are present in both eukaryotes and bacteria. Though eukaryotes have 20 different aminoacyl-tRNA synthetases to couple to 20 amino acids, many bacteria do not have genes for all of these aminoacyl-tRNA synthetases. Despite this, they still use all 20 amino acids to synthesize their proteins. For instance, some bacteria do not have the gene encoding the enzyme that couples glutamine with its partner tRNA. In these organisms, one enzyme adds glutamic acid to all of the...
tRNA Activation
Aminoacyl-tRNA synthetases are present in both eukaryotes and bacteria. Though eukaryotes have 20 different aminoacyl-tRNA synthetases to couple to 20 amino acids, many bacteria do not have genes for all of these aminoacyl-tRNA synthetases. Despite this, they still use all 20 amino acids to synthesize their proteins. For instance, some bacteria do not have the gene encoding the enzyme that couples glutamine with its partner tRNA. In these organisms, one enzyme adds glutamic acid to all of the...
Allosteric Proteins-ATCase
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...


