Structural biology of biotin-dependent carboxylases
生物素依赖性羧化酶的结构生物学
基本信息
- 批准号:8008942
- 负责人:
- 金额:$ 6.2万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-01-15 至 2010-03-31
- 项目状态:已结题
- 来源:
- 关键词:AcidityActive SitesAddressAffectAmino Acid SubstitutionAmino AcidsAnimal WelfareBacteriaBibliographyBindingBiochemicalBiological ModelsBiotinCarbon DioxideCarboxyltransferasesCatabolismCatalysisCatalytic DomainCobaltComplexCountryCritiquesCrystallizationDataDecarboxylationDependenceDiseaseEnvironmentEnvironmental ImpactEnzymesEquipmentFatty AcidsGenesGluconeogenesisHumanIACUCImageIn VitroInternationalIonsLabelLeadLigand BindingLigandsMetabolicMetabolic DiseasesMetabolic PathwayMethodsMethylmalonyl-CoA carboxyltransferaseMissense MutationMonitorMultienzyme ComplexesMutationN1&apos-carboxybiotinNatureOutcomeOxaloacetatesPatientsPlayPopulationPreparationPrincipal InvestigatorPropionic AcidsProteinsProtonsPublishingPyruvatePyruvatesRaman Spectrum AnalysisReactionRelative (related person)ResearchResearch DesignResearch Ethics CommitteesResolutionResourcesRoleSamplingShapesSite-Directed MutagenesisSpectrum AnalysisStaining methodStainsStretchingStructureTechniquesTestingVertebratesYeastsabstractingbiotin 2carbon dioxide transportcarboxylationcofactordeprotonationdesigndevelopmental diseaseenolateenzyme deficiencyexpirationhuman subjectinhibitor/antagonistketotic hyperglycinemialactic acidemiamethylmalonyl-CoA decarboxylasenoveloxidationparticleprogramspropionyl-coenzyme Aprotein foldingresearch studyresponsestructural biologytiglyl-coenzyme Atool
项目摘要
Biotin-dependent carboxylases use a covalently attached biotin cofactor to transport carbon dioxide as carboxybiotin. Four human biotin-dependent
carboxylases have been identified, and play central roles in metabolic pathways such as oxidation of odd-chain fatty acids, catabolism of branched amino acids, fatty acid synthesis, and gluconeogenesis.
The bacterial transcarboxylase enzyme has long served as a model system for the human biotindependent carboxylases. This proposal focuses on structure-function studies of transcarboxylase and on two human enzymes, propionyl coenzyme A carboxylase and methylcrotonoyl coenzyme A
carboxylase. The broad objective is to provide structural information for these enzymes in order to better understand their assembly as multi-enzyme complexes and their mechanisms of catalytic activity. The specific aims are to: 1. To probe the chemistry and mechanism of the transcarboxylase
active sites with structural studies of the isolated 12S and 5S subunits. Crystals of the isolated subunits bound to substrate, product, or cofactor will be studied by X-ray crystallography and Raman crystallography. Site- directed mutagenesis will be used to probe the importance of residues highlighted by structural studies. 2. To probe the molecular architecture of the intact transcarboxylase multienzyme complex by X-ray crystallography and electron microscopy. 3. To investigate the crystal structure of human propionyl coenzyme A carboxylase and to model the possible structural consequences of deficiency mutations in the metabolic disorder propionic acidemia. 4. To investigate the crystal structure
of the human methylcrotonyl coenzyme A carboxylase beta subunit and to model the possible structural consequences of deficiency patients with the metabolic disorder 3-methylcrotonylglycinuria. Relevance: Biotin-dependent enzymes are important in human metabolism. Mutations which alter their genes are found in patients with metabolic and developmental disorders. Investigating the structures of these enzymes will aid understanding of how these proteins assemble and function, and help explain how mutations may cause disease.
生物素依赖性羧化酶使用共价连接的生物素辅因子将二氧化碳作为羧基生物素运输。四种人类生物素依赖性
羧化酶已被鉴定,并且在代谢途径中发挥核心作用,例如奇数链脂肪酸的氧化、支链氨基酸的分解代谢、脂肪酸合成和糖异生。
细菌转羧酶长期以来一直作为人类生物素依赖性羧化酶的模型系统。该提案重点关注转羧酶和两种人类酶(丙酰辅酶 A 羧化酶和甲基巴豆酰辅酶 A)的结构功能研究
羧化酶。广泛的目标是提供这些酶的结构信息,以便更好地了解它们作为多酶复合物的组装及其催化活性机制。具体目标是: 1. 探讨转羧酶的化学性质和作用机制
活性位点以及分离的 12S 和 5S 亚基的结构研究。与底物、产物或辅因子结合的分离亚基的晶体将通过 X 射线晶体学和拉曼晶体学进行研究。定点诱变将用于探讨结构研究强调的残基的重要性。 2. 通过X射线晶体学和电子显微镜探测完整转羧酶多酶复合物的分子结构。 3. 研究人丙酰辅酶 A 羧化酶的晶体结构,并模拟代谢紊乱丙酸血症中缺陷突变可能产生的结构后果。 4. 研究晶体结构
人类甲基巴豆酰辅酶 A 羧化酶 β 亚基的研究,并模拟患有代谢性疾病 3-甲基巴豆酰甘氨酸尿症的缺陷患者可能的结构后果。相关性:生物素依赖性酶在人体新陈代谢中很重要。在患有代谢和发育障碍的患者中发现了改变其基因的突变。研究这些酶的结构将有助于了解这些蛋白质如何组装和发挥作用,并有助于解释突变如何导致疾病。
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 }}
VIVIEN YEE其他文献
VIVIEN YEE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('VIVIEN YEE', 18)}}的其他基金
CRYSTAL STRUCTURE OF A TRANSCARBOXYLASE (TC) MULTIENZYME COMPLEX
转羧酶 (TC) 多酶复合物的晶体结构
- 批准号:
8169332 - 财政年份:2010
- 资助金额:
$ 6.2万 - 项目类别:
TRANSCARBOXYLASE, A 12MDA MULTIENZYME COMPLEX
转羧酶,一种 12MDA 多酶复合物
- 批准号:
7726278 - 财政年份:2008
- 资助金额:
$ 6.2万 - 项目类别:
Structural biology of biotin-dependent carboxylases
生物素依赖性羧化酶的结构生物学
- 批准号:
7546538 - 财政年份:2008
- 资助金额:
$ 6.2万 - 项目类别:
Structural biology of biotin-dependent carboxylases
生物素依赖性羧化酶的结构生物学
- 批准号:
8009397 - 财政年份:2008
- 资助金额:
$ 6.2万 - 项目类别:
TRANSCARBOXYLASE, A 12MDA MULTIENZYME COMPLEX
转羧酶,一种 12MDA 多酶复合物
- 批准号:
7602345 - 财政年份:2007
- 资助金额:
$ 6.2万 - 项目类别:
CRYSTALLOGRAPHIC STUDY OF HUMAN RECOMBINANT FACTOR XIII
人类重组因子 XIII 的晶体学研究
- 批准号:
6658548 - 财政年份:2002
- 资助金额:
$ 6.2万 - 项目类别:
CRYSTALLOGRAPHIC STUDY OF HUMAN RECOMBINANT FACTOR XIII
人类重组因子 XIII 的晶体学研究
- 批准号:
6586581 - 财政年份:2002
- 资助金额:
$ 6.2万 - 项目类别:
相似海外基金
NSF-BSF: Towards a Molecular Understanding of Dynamic Active Sites in Advanced Alkaline Water Oxidation Catalysts
NSF-BSF:高级碱性水氧化催化剂动态活性位点的分子理解
- 批准号:
2400195 - 财政年份:2024
- 资助金额:
$ 6.2万 - 项目类别:
Standard Grant
Collaborative Research: Beyond the Single-Atom Paradigm: A Priori Design of Dual-Atom Alloy Active Sites for Efficient and Selective Chemical Conversions
合作研究:超越单原子范式:双原子合金活性位点的先验设计,用于高效和选择性化学转化
- 批准号:
2334970 - 财政年份:2024
- 资助金额:
$ 6.2万 - 项目类别:
Standard Grant
Collaborative Research: Beyond the Single-Atom Paradigm: A Priori Design of Dual-Atom Alloy Active Sites for Efficient and Selective Chemical Conversions
合作研究:超越单原子范式:双原子合金活性位点的先验设计,用于高效和选择性化学转化
- 批准号:
2334969 - 财政年份:2024
- 资助金额:
$ 6.2万 - 项目类别:
Standard Grant
Mechanochemical synthesis of nanocarbon and design of active sites for oxygen reducton/evolution reactions
纳米碳的机械化学合成和氧还原/演化反应活性位点的设计
- 批准号:
23K04919 - 财政年份:2023
- 资助金额:
$ 6.2万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Creation of porous inorganic frameworks with controlled structure of metal active sites by the building block method.
通过积木法创建具有金属活性位点受控结构的多孔无机框架。
- 批准号:
22KJ2957 - 财政年份:2023
- 资助金额:
$ 6.2万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Catalysis of Juxaposed Active Sites Created in Nanospaces and Their Applications
纳米空间中并置活性位点的催化及其应用
- 批准号:
23K04494 - 财政年份:2023
- 资助金额:
$ 6.2万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Generation of carbon active sites by modifying the oxygen containing functional groups and structures of carbons for utilizing to various catalytic reactions.
通过修饰碳的含氧官能团和结构来产生碳活性位点,用于各种催化反应。
- 批准号:
23K13831 - 财政年份:2023
- 资助金额:
$ 6.2万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
CAREER: CAS: Understanding the Chemistry of Palladium and Silyl Compounds to Design Catalyst Active Sites
职业:CAS:了解钯和甲硅烷基化合物的化学性质以设计催化剂活性位点
- 批准号:
2238379 - 财政年份:2023
- 资助金额:
$ 6.2万 - 项目类别:
Continuing Grant
CAS: Collaborative Research: Tailoring the Distribution of Transient vs. Dynamic Active Sites in Solid-Acid Catalysts and Their Impacts on Chemical Conversions
CAS:合作研究:定制固体酸催化剂中瞬时活性位点与动态活性位点的分布及其对化学转化的影响
- 批准号:
2154399 - 财政年份:2022
- 资助金额:
$ 6.2万 - 项目类别:
Standard Grant
Engineering of Active Sites in Heterogeneous Catalysts for Sustainable Chemical and Fuel Production.
用于可持续化学和燃料生产的多相催化剂活性位点工程。
- 批准号:
RGPIN-2019-06633 - 财政年份:2022
- 资助金额:
$ 6.2万 - 项目类别:
Discovery Grants Program - Individual