Structure and function of RNase P
RNase P 的结构和功能
基本信息
- 批准号:7213525
- 负责人:
- 金额:$ 22.93万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1998
- 资助国家:美国
- 起止时间:1998-01-01 至 2010-12-31
- 项目状态:已结题
- 来源:
- 关键词:Active SitesAddressBacteriaBindingBiochemicalBiologicalBiological ModelsBiological ProcessCatalysisCatalytic RNACellsChargeChemical StructureChemicalsCollaborationsComplexDNA Sequence RearrangementEnzymesEquilibriumEscherichia coliGlycine decarboxylaseHoloenzymesHumanHydrolysisInvestigationIonsIsotopesKineticsLearningLeftLinkMalignant NeoplasmsMass Spectrum AnalysisMetalsMethodsModelingModificationNatureOxygenPathway interactionsPeptidesPersonal SatisfactionPhysiologyPlayProcessProtein BindingProtein DynamicsProtein SubunitsProteinsRNARNA ProcessingRNA-Protein InteractionRNase PRaman Spectrum AnalysisRangeReactionResearchResolutionRibonucleoproteinsRoleSiteSpecificityStagingStructureSystemTechnologyTimeTransfer RNAViralVirusWorkbasecatalystdeprotonationdivalent metalinhibitor/antagonistinsightinterestnovelnovel strategiesphosphodiesterphosphorothioateprotein structureresearch studyself assemblystopped-flow fluorescencetRNA Precursortherapeutic target
项目摘要
DESCRIPTION (provided by applicant): Human cells depend on RNA to perform central roles in information transfer and the synthesis of other biomolecules. At several critical points in these processes RNA itself acts as a catalyst. Because of their essential role, these molecules are important targets for anti-cancer and anti-viral therapies. However, the RNAs in cells and viruses require the binding of specific proteins to function. Thus, a complete understanding of physiology of RNA requires both an understanding of the structural and catalytic features of the RNA molecules themselves, as well as the roles that protein binding plays in activating and modulating their biological activity. However, our understanding of RNA catalytic mechanism is still emerging and the range and functional effects of conformational changes in the assembly of most RNA-protein complexes has been difficult to achieve.
Our investigations focus on understanding how the RNA and protein subunits of bacterial RNase P work together to achieve biological catalysis. RNase P is a ubiquitous and highly conserved ribonucleoprotein enzyme that generates the mature 5' ends of tRNAs. This ribonucleoprotein consists of a single protein bound to a larger catalytic RNA subunit termed P RNA, and is thus an excellent model system for exploring fundamental aspects of RNA catalysis and the coordinated biological function of RNA and protein. We are using this system to address three fundamental questions: 1. What is the mechanism of RNase P catalyzed phosphodiester hydrolysis?; 2. How do the RNA and protein subunits collaborate to achieve catalysis?; and, 3. What is the pathway by which the RNA and protein subunits fold into a functional complex? The answers to these questions will contribute to our understanding of biological catalysis and ribonucleoprotein function and in the long term provide the basis for inhibitor-based therapeutics that target RNAs.
描述(申请人提供):人类细胞依赖RNA在信息传递和其他生物分子的合成中发挥中心作用。在这些过程中的几个关键点上,RNA本身起到了催化剂的作用。由于它们的基本作用,这些分子是抗癌和抗病毒治疗的重要靶点。然而,细胞和病毒中的RNA需要特定蛋白质的结合才能发挥作用。因此,要完全理解RNA的生理学,既需要了解RNA分子本身的结构和催化特性,也需要了解蛋白质结合在激活和调节其生物活性方面所起的作用。然而,我们对RNA催化机制的了解还在不断加深,大多数RNA-蛋白质复合体组装过程中构象变化的范围和功能效应还很难实现。
我们的研究重点是了解细菌RNaseP的RNA和蛋白质亚基是如何共同作用实现生物催化的。RNaseP是一种普遍存在的高度保守的核糖核蛋白酶,它能产生tRNAs的成熟5‘端。这种核糖核蛋白由一个单一的蛋白质与一个更大的催化RNA亚单位结合组成,称为P RNA,因此是探索RNA催化的基本方面以及RNA和蛋白质的协调生物功能的优秀模型系统。我们正在利用这个系统来解决三个基本问题:1.RNaseP催化磷酸二酯水解的机制是什么?2.RNA和蛋白质亚单位是如何协同实现催化作用的?以及,3.RNA和蛋白质亚单位折叠成功能复合体的途径是什么?这些问题的答案将有助于我们理解生物催化和核糖核蛋白的功能,并从长远来看,为靶向RNA的基于抑制剂的治疗提供基础。
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 E. HARRIS其他文献
MICHAEL E. HARRIS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 E. HARRIS', 18)}}的其他基金
Specificity in Substrate Recognition and Catalysis by RNA Processing Enzymes
RNA 加工酶对底物识别和催化的特异性
- 批准号:
10190963 - 财政年份:2018
- 资助金额:
$ 22.93万 - 项目类别:
Specificity in Substrate Recognition and Catalysis by RNA Processing Enzymes
RNA 加工酶对底物识别和催化的特异性
- 批准号:
10434828 - 财政年份:2018
- 资助金额:
$ 22.93万 - 项目类别:
Mechanistic Enzymology of Phosphoryl Transfer Enzymes
磷酰基转移酶的机械酶学
- 批准号:
8697309 - 财政年份:2011
- 资助金额:
$ 22.93万 - 项目类别:
Mechanistic enzymology of phosphoryl transfer enzymes
磷酰基转移酶的机械酶学
- 批准号:
8329007 - 财政年份:2011
- 资助金额:
$ 22.93万 - 项目类别:
Mechanistic Enzymology of Phosphoryl Transfer Enzymes
磷酰基转移酶的机械酶学
- 批准号:
9253409 - 财政年份:2011
- 资助金额:
$ 22.93万 - 项目类别:
Mechanistic Enzymology of Phosphoryl Transfer Enzymes
磷酰基转移酶的机械酶学
- 批准号:
9105386 - 财政年份:2011
- 资助金额:
$ 22.93万 - 项目类别:
Mechanistic Enzymology of Phosphoryl Transfer Enzymes
磷酰基转移酶的机械酶学
- 批准号:
8909608 - 财政年份:2011
- 资助金额:
$ 22.93万 - 项目类别:
Mechanistic enzymology of phosphoryl transfer enzymes
磷酰基转移酶的机械酶学
- 批准号:
8184531 - 财政年份:2011
- 资助金额:
$ 22.93万 - 项目类别:
Determination of enzyme isotope effects by tandem ESI-Q/TOF mass spectrometry
通过串联 ESI-Q/TOF 质谱测定酶同位素效应
- 批准号:
7191481 - 财政年份:2007
- 资助金额:
$ 22.93万 - 项目类别:
Determination of enzyme isotope effects by tandem ESI-Q/TOF mass spectrometry
通过串联 ESI-Q/TOF 质谱测定酶同位素效应
- 批准号:
7345472 - 财政年份:2007
- 资助金额:
$ 22.93万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 22.93万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 22.93万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 22.93万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 22.93万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 22.93万 - 项目类别:
Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 22.93万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 22.93万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 22.93万 - 项目类别:
EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 22.93万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 22.93万 - 项目类别:
Research Grant