Confining Metal Complexes within Protein Hosts: Models for Metalloprotein Active Sites
Confining Metal Complexes within Protein Hosts: Models for Metalloprotein Active Sites
批准号:
10365553
负责人:
Andrew S. Borovik
金额:
$30.11万
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
未结题
起止时间:
2017-06-15 至 2025-08-31
关键词:
Active SitesAffectAgingBindingBiomimeticsBiotinChemicalsComparative StudyComplexDetectionDevelopmentDioxygenEngineeringEnsureEnvironmentExcisionFunctional disorderGlareGoalsHealthHumanHydrogen BondingImmobilizationLinkLocationMagnetismMetalloproteinsMetalsMethane hydroxylaseMethodsMixed Function OxygenasesModelingMolecularMolecular BiologyMononuclearMutationOperating SystemOxidation-ReductionOxidesOxygenasesPositioning AttributeProcessPropertyProteinsRegulationReproducibilityResearchRibonucleotide ReductaseScienceSideSiteStreptavidinStructureStructure-Activity RelationshipSynthesis ChemistrySystemTechnologyTyrosineWateraqueouschemical propertycofactordesignimprovedmetal complexphysical propertyprogramsprotein functionprotein structure functionsmall moleculestructural biologytool
中文摘要
这项研究将开发方法来模拟金属蛋白中的活性位点,
确定蛋白质如何激活双氧的基本结构-功能关系,
这一过程强烈影响人类健康和衰老。人工金属蛋白将被制备
利用生物素-链霉亲和素技术作为工具,确保特异性和可再现的放置
蛋白质宿主中的合成金属复合物。这种方法被认为是一种有效的
一种模拟天然金属蛋白中活性位点的关键特性的方法,包括位点
隔离物种,调节初级协调领域,控制
金属配合物周围的微环境。许多仿生生物的一个明显弱点是
系统的一个缺点是它们调节金属中心周围微环境的能力有限。
没有一个化学系统是孤立地运行而不与当地环境相互作用的。有
越来越多的来自结构生物学的证据表明,微环境,
金属配合物,包括次级配位球,具有深远的影响,
蛋白质功能的范围从调节物理性质到递送反应物,
移除产品。
我们的论点是,对微环境的更大调节将导致更好的
了解蛋白质的功能。有人进一步认为,
本申请中提出的基本分析远远超出了对
在分子水平上的选择性/效率-它们对于所有类型的
平台,提供必要的信息,这仍然是缺乏的发展,
功能强大的系统。
我们提出了一种制备人工金属蛋白的方法,
蛋白质宿主内的合成复合物来调节初级和次级
固定金属中心周围的配位球。调节这些的能力
蛋白质内的配位球将产生系统的结构-功能关系
这将导致更好地理解直接联系到的化学过程,
人体健康
英文摘要
This research will develop methods to model active sites in metalloproteins for the purpose of
determining fundamental structure-function relationships for how proteins activate dioxygen, a
process that strongly impacts human health and aging. Artificial metallproteins will be prepared
utilizing biotin-streptavidin technology as a tool to ensure specific and reproducible placement
of synthetic metal complexes within protein hosts. This approach is proposed to be an effective
method to model key properties of the active sites in native metalloproteins, including site
isolation of species, regulation of the primary coordination sphere, and control of the
microenvironments around the metal complexes. One glaring weakness of many biomimetic
systems is their limited ability to regulate the microenvironments that surround metal centers.
No chemical system operates in isolation without interacting with its local environment. There is
a growing body of evidence from structural biology that the microenvironment, a space around
metal complexes that comprises the secondary coordination sphere, has profound effects on
protein function that ranges from modulation of physical properties to delivery of reactants and
removal of products.
It is our contention that the greater regulation of microenvironments will lead to better
understanding of protein function. It is further maintained that the benefits gained from
fundamental analyses as proposed in this application extend well beyond improvements in
selectivities/efficiencies at the molecular level – they are transformative for all types of
platforms, providing the requisite information that is still missing for the development of
highly functional systems.
We propose an approach for preparing artificial metalloproteins that allows for the confinement
of synthetic complexes within protein hosts to regulate both the primary and secondary
coordination spheres about the immobilized metal centers. The ability to regulate these
coordination spheres within a protein will produce systematic structure-function relationships
that will lead to an improved understanding of chemical processes that are directly linked to
human health.
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会议论文
Confining Metal Complexes within Protein Hosts: Models for Metalloprotein Active Sites
-
批准号:9383464
-
项目类别:
-
资助金额:$27.73万
-
财政年份:2017
-
负责人:Andrew S. Borovik
-
依托单位:
Confining Metal Complexes within Protein Hosts: Models for Metalloprotein Active Sites
-
批准号:10677010
-
项目类别:
-
资助金额:$29.86万
-
财政年份:2017
-
负责人:Andrew S. Borovik
-
依托单位:
CATALYTIC METALLO-BIOMIMETIC SITES IN POROUS HOSTS
-
批准号:6525497
-
项目类别:
-
资助金额:$16.79万
-
财政年份:1999
-
负责人:Andrew S. Borovik
-
依托单位:
CATALYTIC METALLO-BIOMIMETIC SITES IN POROUS HOSTS
-
批准号:6181045
-
项目类别:
-
资助金额:$15.78万
-
财政年份:1999
-
负责人:Andrew S. Borovik
-
依托单位:
CATALYTIC METALLO/BIOMIMETIC SITES IN POROUS HOSTS
-
批准号:2734851
-
项目类别:
-
资助金额:$17.53万
-
财政年份:1999
-
负责人:Andrew S. Borovik
-
依托单位:
CATALYTIC METALLO-BIOMIMETIC SITES IN POROUS HOSTS
-
批准号:6386380
-
项目类别:
-
资助金额:$16.24万
-
财政年份:1999
-
负责人:Andrew S. Borovik
-
依托单位:
HELICAL AND CAVITY MOTIFS ABOUT METAL IONS
-
批准号:2188850
-
项目类别:
-
资助金额:$7.32万
-
财政年份:1994
-
负责人:Andrew S. Borovik
-
依托单位:
HELICAL AND CAVITY MOTIFS ABOUT METAL IONS
-
批准号:2685029
-
项目类别:
-
资助金额:$8.83万
-
财政年份:1994
-
负责人:Andrew S. Borovik
-
依托单位:
Hydrogen Bonding Cavity Motifs about Metal Ions
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批准号:7385713
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项目类别:
-
资助金额:$23.2万
-
财政年份:1994
-
负责人:Andrew S. Borovik
-
依托单位:
Hydrogen Bonding Cavity Motifs About Metal Ions
-
批准号:9978348
-
项目类别:
-
资助金额:$41.33万
-
财政年份:1994
-
负责人:Andrew S. Borovik
-
依托单位:
Hydrogen Bonding Cavity Motifs About Metal Ions
-
批准号:7751208
-
项目类别:
-
资助金额:$26.12万
-
财政年份:1994
-
负责人:Andrew S. Borovik
-
依托单位:
Hydrogen Bonding Cavity Motifs About Metal Ions
-
批准号:8018070
-
项目类别:
-
资助金额:$25.62万
-
财政年份:1994
-
负责人:Andrew S. Borovik
-
依托单位:
Hydrogen Bonding Cavity Motifs about Metal Ions
-
批准号:6734740
-
项目类别:
-
资助金额:$25.39万
-
财政年份:1994
-
负责人:Andrew S. Borovik
-
依托单位:
Hydrogen Bonding Cavity Motifs About Metal Ions
-
批准号:9028171
-
项目类别:
-
资助金额:$37.92万
-
财政年份:1994
-
负责人:Andrew S. Borovik
-
依托单位:
Hydrogen Bonding Cavity Motifs About Metal Ions
-
批准号:10547742
-
项目类别:
-
资助金额:$39.2万
-
财政年份:1994
-
负责人:Andrew S. Borovik
-
依托单位:
Hydrogen Bonding Cavity Motifs about Metal Ions
-
批准号:6876572
-
项目类别:
-
资助金额:$25.04万
-
财政年份:1994
-
负责人:Andrew S. Borovik
-
依托单位:
HYDROGEN BONDING CAVITY MOTIFS ABOUT METAL IONS
-
批准号:6179732
-
项目类别:
-
资助金额:$17.08万
-
财政年份:1994
-
负责人:Andrew S. Borovik
-
依托单位:
Artificial Metalloproteins: Confining Metal Complexes within Protein Hosts. (Orig
-
批准号:8662429
-
项目类别:
-
资助金额:$4.33万
-
财政年份:1994
-
负责人:Andrew S. Borovik
-
依托单位:
HYDROGEN BONDING CAVITY MOTIFS ABOUT METAL IONS
-
批准号:8599468
-
项目类别:
-
资助金额:$40.2万
-
财政年份:1994
-
负责人:Andrew S. Borovik
-
依托单位:
Hydrogen Bonding Cavity Motifs About Metal Ions
-
批准号:10301348
-
项目类别:
-
资助金额:$41.33万
-
财政年份:1994
-
负责人:Andrew S. Borovik
-
依托单位:
海外基金