艾滋病毒-1LTR的主要G-四重体形式显示包含干环的 (3 + 1) 折叠拓
Elena Butovskaya1,2, Brahim Heddi1,3, Blaž Bakalar1
1School of Physical and Mathematical Sciences , Nanyang Technological University , Singapore 637371 , Singapore.
Journal of the American Chemical Society
|October 10, 2018
概括
研究人员确定了HIV-1促进体中的特定G-四重复 (LTR-III) 的NMR结构. 这种结构揭示了独特的混合四重复模因,为抗病毒药物开发提供了潜在的新目标.
科学领域:
- 结构生物学
- 病毒学
- 医学化学
背景情况:
- 在基因组中发现的非正规的核酸结构,包括像HIV-1这样的病毒.
- 在HIV-1长终端重复 (LTR) 促进体中,富含G的序列形成了调节病毒转录的G四重复.
- 通过配体稳定这些G-四重复,减少病毒的产生,这表明了潜在的抗病毒策略.
研究的目的:
- 确定LTR-III G-四重体的高分辨率结构,这是HIV-1 LTR促进体的主要构造.
- 描述LTR-III的独特结构特征,用于潜在的药物向.
- 探索LTR-III G-四重复作为抗病毒疗法的新目标.
主要方法:
- 用核磁共振 (NMR) 光谱来确定LTR-III的三维结构.
- 结构分析的重点是确定独特的动机和潜在的药物结合点.
- 实验室研究证实LTR-III是主要的G-四重体形状.
主要成果:
- LTR-III的核磁共振结构显示出一个独特的四重复杂结构.
- 这种混合结构包括一个 (3+1) G-四架,具有明显的环形,包括一个对角环形的双杆.
- 一个值得注意的特点是四重复交叉路口,呈现出一种新的可准动机.
结论:
- 解决了LTR-III的NMR结构,为HIV-1 LTR中的G-四重复形成提供了关键的见解.
- 独特的四重复杂混合结构,特别是结合,是开发选择性抗病毒药物的有吸引力的目标.
- 这种结构信息可以指导新疗法的设计,通过向LTR G四重复体来抑制病毒循环.
相关概念视频
LTR Retrotransposons
19.7K
LTR retrotransposons are class I transposable elements with long terminal repeats flanking an internal coding region. These elements are less abundant in mammals compared to other class I transposable elements. About 8 percent of human genomic DNA comprises LTR retrotransposons. Some of the common examples of LTR retrotransposons are Ty elements in yeast and Copia elements in Drosophila.
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...
19.7K
Non-LTR Retrotransposons
13.4K
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
13.4K
SN1 Reaction: Stereochemistry
10.3K
This lesson provides an in-depth discussion of the stereochemical outcomes in an SN1 reaction.
In the first step of an SN1 reaction, the bond between the electrophilic carbon and the leaving group ionizes to generate the carbocation intermediate. The second step of the mechanism is the nucleophilic attack.
In the formed carbocation, the positively charged carbon is sp2 hybridized with a trigonal planar geometry. As all the three substituents lie on the same plane, a plane of symmetry for the...
In the first step of an SN1 reaction, the bond between the electrophilic carbon and the leaving group ionizes to generate the carbocation intermediate. The second step of the mechanism is the nucleophilic attack.
In the formed carbocation, the positively charged carbon is sp2 hybridized with a trigonal planar geometry. As all the three substituents lie on the same plane, a plane of symmetry for the...
10.3K
SN1 Reaction: Kinetics
9.6K
In an SN2 reaction, the reaction rate depends on both the type of nucleophile and the substrate. A hindered tertiary alkyl halide is practically inert to the SN2 mechanism despite using a strong nucleophile.
However, Sir Christopher Ingold and Edward D. Hughes, who studied the kinetics of various nucleophilic substitution reactions, noticed that a tertiary alkyl halide does undergo a nucleophilic substitution reaction in the presence of a weak nucleophile. While studying the substitution...
However, Sir Christopher Ingold and Edward D. Hughes, who studied the kinetics of various nucleophilic substitution reactions, noticed that a tertiary alkyl halide does undergo a nucleophilic substitution reaction in the presence of a weak nucleophile. While studying the substitution...
9.6K
SN1 Reaction: Mechanism
14.3K
Kinetic studies of ionization of a tertiary halide in a protic solvent suggest that only the substrate participates in the rate-determining step (slow step). The nucleophile is involved only after the slowest step. The SN1 reaction takes place in a multiple-step mechanism.
Firstly, the haloalkane ionizes to generate a carbocation intermediate and a halide ion. This heterolytic cleavage is highly endothermic with large activation energy. The ionization of the substrate, facilitated by a...
Firstly, the haloalkane ionizes to generate a carbocation intermediate and a halide ion. This heterolytic cleavage is highly endothermic with large activation energy. The ionization of the substrate, facilitated by a...
14.3K
Acidity of 1-Alkynes
11.2K
The acidic strength of hydrocarbons follows the order: Alkynes > Alkenes > Alkanes. The strength of an acid is commonly expressed in units of pKa — the lower the pKa, the stronger the acid. Among the hydrocarbons, terminal alkynes have lower pKa values and are, therefore, more acidic. For example, the pKa values for ethane, ethene, and acetylene are 51, 44, and 25, respectively, as shown here.
11.2K


