De novo designed metalloproteins as a new generation of artificial hydrogenases
从头设计金属蛋白作为新一代人工氢化酶
基本信息
- 批准号:10360279
- 负责人:
- 金额:$ 41.95万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-20 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:Active SitesAffectBioinorganic ChemistryBiotechnologyCarbonCatalysisChemistryComplexDependenceDevelopmentElectrochemistryElectron TransportEnvironmentEnzymesFilmFluorescenceFutureGasesGenerationsGoalsHydrogen BondingHydrogenaseKineticsLocationMentorsMetal Binding SiteMetalloproteinsMetalsMethodsMississippiModelingMononuclearMultienzyme ComplexesNatural ResourcesOrganismOutcomeOutcome StudyOxidation-ReductionPathway interactionsPeptidesPhasePhotosensitizing AgentsProductionPropertyProtein EngineeringProteinsReactionResearchResearch ActivityRoleScaffolding ProteinScienceSecuritySiteSolidSourceSpectroscopy, Fourier Transform InfraredSpectrum AnalysisStructureSulfhydryl CompoundsSunlightSurfaceSystemTestingTitrationsTrainingUniversitiesWaterWorkabsorptionanalogbasebiophysical techniquescarbon emissionscareercatalystcofactordesigndimerfinessegraduate studentimproved functioninginsightmetallicitymetalloenzymenickel-iron hydrogenasenovelprogramsscaffoldsmall moleculesynergismundergraduate student
项目摘要
PROJECT SUMMARY/ABSTRACT
Hydrogenases are complex, metal-containing enzymes that generate energy for certain organisms by
catalyzing the reversible interconversion between H+ and H2 gas. Unraveling the intricate details about the
function of these enzymes will significantly advance the H2-based, carbon-neutral alternative energy
production. However, the complexity of these enzymes due to the presence of multiple metallic cofactors, low
production yield, and deactivation, makes studying these enzymes challenging. Our long term goals are to
design artificial biomolecular hydrogenases (ArHs) as simpler functional analogs of these metalloenzymes.
De novo metalloprotein design is an appealing and well-established approach to model complex
metalloproteins within minimal protein scaffolds. Although the designed systems are less complex, they serve
as water-soluble functional analogs of the native metalloenzymes and provide a functional view of the
chemistry. Employing this approach, we propose to pursue three Specific Aims describing the overall design
principles and functional/mechanistic attributes of the ArHs inspired by the [NiFe] hydrogenases. The overall
objectives of this proposal are: i) to design mononuclear (Ni), binuclear (Ni-Fe), and multinuclear (Ni3) active
sites within suitable de novo scaffolds; ii) characterize the physical and catalytic properties of the ArHs; iii)
determine the timescales of electron transfer; iv) outline the H+ transfer pathways; v) characterize the reaction
intermediates; and vi) elucidate how metals and protein scaffold work in synergy to influence the
properties/reactivity, such that a holistic mechanistic view of H-H bond formation can be attained. Our strong
preliminary results presented here attest that our objectives are achievable.
Collectively, the results from this proposed work will impact the fields of metalloprotein design, bioinorganic
chemistry, and alternative energy research. A novel class of ArHs will emerge, which will provide functional
vignettes into the working principles of H+ reduction pertaining to the native enzymes. The modular design
parameters and outcomes from this study will enable us to prepare biosynthetic catalysts with novel properties
and functions in the future.
项目总结/摘要
氢化酶是一种复杂的含金属酶,通过以下方式为某些生物体产生能量:
催化H+和H2气体之间的可逆相互转化。解开有关
这些酶的功能将大大推进氢基碳中性替代能源
生产然而,由于存在多种金属辅因子,这些酶的复杂性低,
产率和失活使得研究这些酶具有挑战性。我们的长期目标是
设计人工生物分子氢化酶(ArH)作为这些金属酶的简单功能类似物。
从头金属蛋白设计是一种吸引人的和成熟的方法来模拟复杂的
金属蛋白在最小的蛋白质支架内。虽然设计的系统不太复杂,但它们可以
作为天然金属酶的水溶性功能类似物,
化学.采用这种方法,我们建议追求三个具体目标,描述整体设计
原理和功能/机械属性的ArH启发[NiFe]氢化酶。整体
本提案的目标是:i)设计单核(Ni)、双核(Ni-Fe)和多核(Ni 3)活性
ii)表征ArH的物理和催化性质; iii)
确定电子转移的时间尺度; iv)概述H+转移途径; v)表征反应
中间体;和vi)阐明金属和蛋白质支架如何协同作用以影响蛋白质的合成。
性质/反应性,使得可以获得H-H键形成的整体机理视图。我们强大
这里所介绍的初步结果证明,我们的目标是可以实现的。
总的来说,这项工作的结果将影响金属蛋白设计,生物无机,
化学和替代能源研究。一种新型的ArH将出现,这将提供功能性的
小插曲到H+还原有关的天然酶的工作原理。模块化设计
本研究的参数和结果将使我们能够制备具有新性能的生物合成催化剂
和功能在未来。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Biosynthetic Approaches towards the Design of Artificial Hydrogen-Evolution Catalysts.
生物合成方法用于设计人工氢进化催化剂。
- DOI:10.1002/chem.202001338
- 发表时间:2020-10-01
- 期刊:
- 影响因子:0
- 作者:Prasad P;Selvan D;Chakraborty S
- 通讯作者:Chakraborty S
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