相关实验视频

Updated: Jul 15, 2025

RNA Catalyst as a Reporter for Screening Drugs against RNA Editing in Trypanosomes

RNA Catalyst as a Reporter for Screening Drugs against RNA Editing in Trypanosomes

Published on: July 22, 2014

在非洲试种子体中,苏拉明的作用涉及一种类似RuvB的DNA螺旋酶

Anna Albisetti¹, Silvan Hälg¹, Martin Zoltner²

¹Swiss Tropical and Public Health Institute, Kreuzstrasse 2, 4123, Allschwil, Switzerland; University of Basel, Petersplatz 1, 4001, Basel, Switzerland.

International journal for parasitology. Drugs and drug resistance

|September 27, 2023

概括

非洲试种子体中抗苏拉明的原因是RuvBL1 DNA螺旋酶的突变. 这一发现揭示了该药物的存在.

科学领域:

寄生虫学的寄生虫学
药物耐药性机制药物耐药性机制
分子生物学分子生物学

背景情况:

苏拉明是一种长期以来的治疗非洲睡眠病和surra.
尽管苏拉明的广泛使用,但其确切的作用模式仍然不完全理解.
众所周知,苏拉明与多个蛋白质标相互作用.

研究的目的:

调查非洲试子体中苏拉抗性的基础分子机制.
为了确定参与苏拉的作用和耐药性的特定蛋白质.
探索DNA螺旋酶在苏拉胺敏感性中的作用.

主要方法:

对Trypanosoma brucei rhodesiense进行长期选择,以抗苏拉明.
使用基因分析识别耐药菌株的突变.
逆转基因引入特定突变到对药物敏感的试管体.
通过RNA干扰 (RNAi) 来抑制T. bruceiRuvBL1和RuvBL2基因的表达.
在基因沉默后对试体的表型分析,重点是细胞分裂.

主要成果:

在T. brucei RuvBL1中,在位于ATP结合部位附近的抗胺试体中,发现了一种同卵性点突变 (Isoleucine-312到Valine).
将这种突变引入对药物敏感的试酶体,显著降低了它们对胺的敏感性.
在一个耐药的野外分离物中,在对应的T. evansi RuvBL1残留物中观察到类似的突变 (与Leucine).
通过RNAi对T. brucei RuvBL1或RuvBL2进行沉默,导致细胞在72小时内死亡.
RNAi诱导导致细胞运动缺陷,并积累了含有多个细胞核和动态细胞质的细胞.

结论:

DNA螺旋酶T. brucei RuvBL1在苏拉明对非洲试体的作用中起着至关重要的作用.
在RuvBL1的突变可以赋予抗苏拉明的耐药性,突出其在药物的疗效的重要性.
准RuvBL1或与之相关的蛋白质,如RuvBL2,是对抗胺抗性的潜在策略.

关键词:

药物目标是药物目标.药物耐药性是一种药物耐药性.类似RuvB的1个DNA螺旋酶.苏拉明·苏拉明 (Suramin Suramin) 是一个著名的在Trypanosoma brucei的研究中.松体 evansi 试体 evansi 是一个

更多相关视频

DNAzyme-dependent Analysis of rRNA 2’-O-Methylation

DNAzyme-dependent Analysis of rRNA 2’-O-Methylation

Published on: September 16, 2019

Examination of the Telomere G-overhang Structure in Trypanosoma brucei

Examination of the Telomere G-overhang Structure in Trypanosoma brucei

Published on: January 26, 2011

相关概念视频

DNA Helicases

DNA Helicases

DNA unwinding helicase enzymes are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates...

Transcription Attenuation in Prokaryotes

Transcription Attenuation in Prokaryotes

Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure. Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...

DNA Topoisomerases

DNA Topoisomerases

Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
Types and Mechanism of action
Topoisomerases are divided into two main types. ...

Restarting Stalled Replication Forks

Restarting Stalled Replication Forks

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...

Destabilization of Microtubules

Destabilization of Microtubules

The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...

The Replisome

The Replisome

DNA replication is carried out by a large complex of proteins that act in a coordinated matter to achieve high-fidelity DNA replication. Together this complex is known as the DNA replication machinery or the replisome.
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with...