核糖体A位点的结合模式不同于来自临床病原体的Arm甲基转移酶和天然氨基糖化物生产者
Sonja Obranić1, Fedora Babić2, Marko Močibob3
1University of Zagreb, Faculty of Pharmacy and Biochemistry, Department of Biochemistry and Molecular Biology, A. Kovačića 1, 10000 Zagreb, Croatia; University North, University Centre Varaždin, 104. brigade 1, 42000 Varaždin, Croatia.
International journal of biological macromolecules
|October 31, 2024
概括
氨基糖化物耐药性是一个日益增长的威胁. 这项研究揭示了Arm/Kam甲基转移酶的独特甲基化模式,为打击细菌耐药性提供了新的途径.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 广泛使用氨基糖化物会导致细菌耐药性,这是一个主要的全球健康问题.
- 阿姆/卡姆甲基转移酶通过修改16SrRNA来赋予耐药性,阻碍了抗生素与核糖体的相互作用.
研究的目的:
- 比较临床Arm甲基转移酶与天然生产者的Sgm甲基转移酶的核糖体A位点结合.
- 研究16S rRNA突变对Arm甲基转移酶活性和细菌活性的影响.
- 了解甲基转移酶与核糖体相互作用的结构和进化差异.
主要方法:
- 在大肠杆菌中,16S rRNA在G1405附近的局部定向突变发生.
- 评估混合和均质核糖体群中的细菌生存能力.
- 确定kanamycin的最小抑制度以评估酶活性.
主要成果:
- 与临床Arm甲基转移酶相比,Sgm甲基转移酶表现出独特的甲基化模式.
- 结构分析揭示了Sgm,RmtB和RmtC中关键残留物的独特空间安排.
- 突变影响了细菌的活力和酶活性,随着核糖体群的均性而变化.
结论:
- 和Sgm甲基转移酶表现出不同的核糖体结合和甲基化策略.
- 结构变异突出了抵抗机制的进化分歧.
- 这些发现为开发针对氨基糖化物耐药性的新型抑制剂提供了基础.
相关概念视频
Types of RNA
63.3K
Overview
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
63.3K
Transfer RNA Synthesis
11.9K
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...
11.9K
Allosteric Proteins-ATCase
5.7K
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...
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...
5.7K
Ligand Binding and Linkage
4.8K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
4.8K
Translational Regulation
1
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
1


