通过内部RNA结构对新型小分子识别的分子洞察力
Tianshuo Liu1, Ling Xu1,2, Kevin Chung3
1Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511.
概括
研究人员使用高通量查和冷电子显微镜 (cryo-EM) 开发了一种用于真菌I组内的新型拼接抑制剂. 这项研究揭示了关键的RNA-连接体识别原理和动态RNA对小分子的反应.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 药用化学 医学化学
背景情况:
- 针对RNA的配体的合理设计对于扩展可药物化基因组至关重要,但仍然具有挑战性.
- 为了优化,需要有效的方法来识别和可视化RNA-ligand复合体的命中.
研究的目的:
- 为了识别一种新型拼接抑制剂的真菌I组内.
- 阐明涉及小分子与RNA标结合的分子相互作用和RNA动态.
主要方法:
- 高通量选 (HTS) 用于识别抑制剂的成功.
- 用于优化化合物的药用化学.
- 高分辨率冷电子显微镜 (cryo-EM) 用于对RNA-连接体复合物的结构性确定.
主要成果:
- 一种新的拼接抑制剂被确定用于对抗大型,高度折叠的真菌I组内.
- 冷电磁结构揭示了详细的分子相互作用和合理化的结构-活性关系.
- 观察到RNA构成和金属离子协调中的可塑性,以应对连接体结合.
结论:
- 该研究提供了管理RNA-连接体识别和结合特异性的一般原则.
- 展示了独特的RNA可塑性策略,涉及金属离子和形状变化.
- 突出了整合HTS,药物化学和冷EM用于RNA向药物发现的力量.
相关概念视频
Nucleic Acid Structure
5.9K
The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms a 5′ to 3′ phosphodiester linkage.
DNA Structure
DNA...
DNA Structure
DNA...
5.9K
RNA Structure
4.6K
The basic structure of RNA consists of a string of ribonucleotides attached by phosphodiester bonds. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA) involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three...
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA) involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three...
4.6K
RNA Interference
25.9K
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
25.9K
RNA Splicing
55.9K
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
55.9K
siRNA - Small Interfering RNAs
16.4K
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
16.4K
Nucleic Acids
43.2K
Nucleic acids are the most important macromolecules for the continuity of life. They carry the cell's genetic blueprint and carry instructions for its functioning.
DNA and RNA
The two main types of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). DNA is the genetic material in all living organisms, ranging from single-celled bacteria to multicellular mammals. It is in the nucleus of eukaryotes and in the organelles, chloroplasts, and mitochondria. In prokaryotes,...
DNA and RNA
The two main types of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). DNA is the genetic material in all living organisms, ranging from single-celled bacteria to multicellular mammals. It is in the nucleus of eukaryotes and in the organelles, chloroplasts, and mitochondria. In prokaryotes,...
43.2K


