药物结合残留在真核细胞核糖体中的演变
Lewis I Chan1, Chinenye L Ekemezie1, Charlotte R Brown1
1Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Cell reports
|September 13, 2025
概括
在真核生物中,核糖体的药物结合部位在不同群体之间有很大差异,与细菌相比,它们的区别比人类的区别更大. 这种分歧影响了针对真核病原体的向疗法和研究工具的开发.
科学领域:
- 进化生物学是进化的生物学.
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 针对真核核糖体的药物是关键的研究工具和潜在的治疗方法.
- 了解真核细胞中的核糖体药物结合部位的变异是必不可少的,但缺乏.
- 需要进行比较研究来绘制这些差异.
研究的目的:
- 追踪核糖体中核糖体药物结合残留物的进化史.
- 为了确定与人类相比,在真核细胞群中药物结合部位的分歧程度.
- 为开发血统特定药物提供资源.
主要方法:
- 对核糖体药物结合残留物的基因组学分析.
- 在真核生物血统之间进行比较的基因组学.
- 进化历史的重建.
主要成果:
- 核糖体药物结合部位在真核细胞群中显示出显著的分歧.
- 一些真核细胞群与人类的核糖体药物结合部位的差异比人类与细菌部位的差异要大.
- 药物结合部位的进化模式有很大差异.
结论:
- 线粒体药物结合部位并非在所有真核生物中保存.
- 发现的进化差异可以为针对特定真核寄生虫的向药物的开发提供信息.
- 这项研究为了解不同类型的真核生物中的核糖体与药物相互作用提供了基础.
相关概念视频
Conserved Binding Sites
5.0K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
5.0K
Conserved Binding Sites
1.9K
1.9K
Ribosomes
10.4K
Ribosomes translate genetic information encoded by messenger RNA (mRNA) into proteins. Both prokaryotic and eukaryotic cells have ribosomes. Cells that synthesize large quantities of protein—such as secretory cells in the human pancreas—can contain millions of ribosomes.
Ribosome Structure and Assembly
Ribosomes are composed of ribosomal RNA (rRNA) and proteins. In eukaryotes, rRNA is transcribed from genes in the nucleolus—a part of the nucleus that specializes in ribosome...
Ribosome Structure and Assembly
Ribosomes are composed of ribosomal RNA (rRNA) and proteins. In eukaryotes, rRNA is transcribed from genes in the nucleolus—a part of the nucleus that specializes in ribosome...
10.4K
Ribosomes
74.7K
Ribosomes translate genetic information encoded by messenger RNA (mRNA) into proteins. Both prokaryotic and eukaryotic cells have ribosomes. Cells that synthesize large quantities of protein—such as secretory cells in the human pancreas—can contain millions of ribosomes.
Ribosome Structure and Assembly
Ribosomes are composed of ribosomal RNA (rRNA) and proteins. In eukaryotes, rRNA is transcribed from genes in the nucleolus—a part of the nucleus that specializes in ribosome...
Ribosome Structure and Assembly
Ribosomes are composed of ribosomal RNA (rRNA) and proteins. In eukaryotes, rRNA is transcribed from genes in the nucleolus—a part of the nucleus that specializes in ribosome...
74.7K
Improving Translational Accuracy
14.1K
Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
14.1K
Transfer RNA Synthesis
13.2K
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...
13.2K


