NMR Studies of Retroviral Nucleic Acid Binding Proteins
逆转录病毒核酸结合蛋白的 NMR 研究
基本信息
- 批准号:6851802
- 负责人:
- 金额:$ 31.61万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1989
- 资助国家:美国
- 起止时间:1989-07-01 至 2006-02-28
- 项目状态:已结题
- 来源:
- 关键词:antineoplasticsantiviral agentschemical structure functioncomputer simulationdimergene delivery systemhuman immunodeficiency virus 1intermolecular interactionmass spectrometrymodel design /developmentmolecular sitemurine leukemia virusnuclear magnetic resonance spectroscopynucleic acid structurenucleocapsidphysical modelsite directed mutagenesisstructural biologyvirus RNAvirus assemblyvirus protein
项目摘要
DESCRIPTION (Provided by the applicant): During the past 3-1/2 years we (i)
identified the stem loops of the HIV-1 Psi-RNA packaging signal that have high
affinities for the nucleocapsid (NC) protein; (ii) determined the structures of
NC complexes with HIV-1 Psi-site stem loops SL2 and SL3; (iii) established the
functional roles of the HIV-1 CCHC zinc knuckles and their conserved amino acid
residues; (iv) demonstrated that SL4 does not bind tightly to NC, as had
previously been reported, and proposed a new role for this essential packaging
element; and (v) discovered a novel three dimensional fold in the C-terminal
zinc knuckle of the Mouse Mammary Tumor Virus (MMTV) NC protein. In addition,
we recently (vi) developed a method for overproduction of the recombinant NC
protein from the Moloney Murine Leukemia Virus (MLV), which is the most widely
used vector in human gene therapy trials, and (vii) identified the minimal
portion of MLV Psi-site that is necessary for high-affinity NC binding. Having
completed studies of NC binding to isolated stem loops, we now intend to study
NC interactions with the intact Psi-sites of MLV and HIV- 1. High quality
preliminary NMR spectra have been obtained for the 102 nucleotide NC-binding
domain of the MLV Psi-site (>70 percent assigned at the time of submission),
and numerous intermolecular NOES have been observed in preliminary NMR data
obtained for its complex with NC. Promising preliminary 3D NMR data have also
been obtained for the intact, 116 nucleotide HIV-1 Psi- site, indicating that
structural studies of this 72.4 kDa symmetrical dimer are also feasible.
Studies of RNAs of 100 nucleotides or larger are technically more challenging
than our previous studies with relatively small RNA stem loops. However, the
potential payoff is substantially greater, and promises to provide the first
detailed structural information for the recognition complexes that lead to the
specific packaging of retroviral genomes. Such knowledge should not only
facilitate the development of approaches for the treatment of AIDS and cancer,
but should also assist in the development of MLV as a more effective agent for
the therapeutic delivery of human genes.
描述(由申请人提供):在过去3年半期间,我们(I)
识别出HIV-1 Psi-RNA包装信号的茎环具有高
核衣壳(NC)蛋白的亲和力;(Ii)确定了
与HIV-1 Psi位干环SL2和SL3的NC复合体;(Iii)建立了
HIV-1 CCHC锌指关节及其保守氨基酸的功能作用
残基;(Iv)证明SL4不像以前那样与NC紧密结合
以前曾报道过,并提出了这种基本包装的新角色
元素;以及(V)在C-末端发现了一个新的三维折叠
锌指关节的小鼠乳腺肿瘤病毒(MMTV)NC蛋白。此外,
我们最近开发了一种过量生产重组NC的方法
来自Moloney鼠白血病病毒(MLV)的蛋白质是最广泛的
在人类基因治疗试验中使用的载体,以及(Vii)确定了最小
MLV Psi位点的一部分,是高亲和力NC结合所必需的。拥有
已经完成了NC与孤立茎环结合的研究,现在我们打算研究
与MLV和HIV-1完整Psi位点的NC相互作用
初步获得了102个核苷酸NC结合的核磁共振谱
MLV Psi站点的域名(在提交时分配了70%),
在初步的核磁共振数据中观察到了大量的分子间NO
因其与NC的络合物而获得。有希望的初步3D核磁共振数据也
已经获得了完整的116个核苷酸的HIV-1 Psi位点,表明
这种72.4 kDa对称二聚体的结构研究也是可行的。
研究100个核苷酸或更大的RNA在技术上更具挑战性
与我们之前的研究相比,RNA茎环相对较小。然而,
潜在的回报要大得多,并承诺提供第一个
识别复合体的详细结构信息,这些信息导致
逆转录病毒基因组的特定包装。这样的知识不仅应该
促进制定治疗艾滋病和癌症的方法,
但也应协助将MLV发展为更有效的
人类基因的治疗性传递。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
MICHAEL FINLEY SUMMERS其他文献
MICHAEL FINLEY SUMMERS的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('MICHAEL FINLEY SUMMERS', 18)}}的其他基金
EXPAND PARTICIPATION BY MINORITIES IN BIOMEDICAL SCIENCE
扩大少数族裔对生物医学科学的参与
- 批准号:
2519078 - 财政年份:1996
- 资助金额:
$ 31.61万 - 项目类别:
相似海外基金
Development of a new generation of antiviral agents that are effective against drug-resistant viruses and prevent serious illness and sequelae.
开发新一代抗病毒药物,可有效对抗耐药病毒并预防严重疾病和后遗症。
- 批准号:
23K18186 - 财政年份:2023
- 资助金额:
$ 31.61万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)
A versatile structure-based therapeutic platform for development of VHH-based antitoxin and antiviral agents
一个多功能的基于结构的治疗平台,用于开发基于 VHH 的抗毒素和抗病毒药物
- 批准号:
10560883 - 财政年份:2023
- 资助金额:
$ 31.61万 - 项目类别:
Genetically encoded bicyclic peptide libraries for the discoveryof novel antiviral agents
用于发现新型抗病毒药物的基因编码双环肽库
- 批准号:
10730692 - 财政年份:2021
- 资助金额:
$ 31.61万 - 项目类别:
Design and synthesis of nucleosides to develop antiviral agents and oligonucleotide therapeutics
设计和合成核苷以开发抗病毒药物和寡核苷酸疗法
- 批准号:
21K06459 - 财政年份:2021
- 资助金额:
$ 31.61万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Genetically encoded bicyclic peptide libraries for the discoveryof novel antiviral agents
用于发现新型抗病毒药物的基因编码双环肽库
- 批准号:
10189880 - 财政年份:2021
- 资助金额:
$ 31.61万 - 项目类别:
Computer-aided identification and synthesis of novel broad-spectrum antiviral agents
新型广谱抗病毒药物的计算机辅助鉴定和合成
- 批准号:
2404261 - 财政年份:2020
- 资助金额:
$ 31.61万 - 项目类别:
Studentship
Develop broad-spectrum antiviral agents against COVID-19 based on innate immune response to SARS-CoV-2 infection
基于对 SARS-CoV-2 感染的先天免疫反应,开发针对 COVID-19 的广谱抗病毒药物
- 批准号:
10222540 - 财政年份:2020
- 资助金额:
$ 31.61万 - 项目类别:
Develop broad-spectrum antiviral agents against COVID-19 based on innate immune response to SARS-CoV-2 infection
基于对 SARS-CoV-2 感染的先天免疫反应,开发针对 COVID-19 的广谱抗病毒药物
- 批准号:
10669717 - 财政年份:2020
- 资助金额:
$ 31.61万 - 项目类别:
Association between sedentary lifestyle and liver cancer development in hepatitis C patients treated with direct-acting antiviral agents
接受直接抗病毒药物治疗的丙型肝炎患者久坐的生活方式与肝癌发展之间的关系
- 批准号:
20K10713 - 财政年份:2020
- 资助金额:
$ 31.61万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Develop broad-spectrum antiviral agents against COVID-19 based on innate immune response to SARS-CoV-2 infection
基于对 SARS-CoV-2 感染的先天免疫反应,开发针对 COVID-19 的广谱抗病毒药物
- 批准号:
10174522 - 财政年份:2020
- 资助金额:
$ 31.61万 - 项目类别: