Unraveling the dynamics that enable unusual heme enzyme reactivity
揭示血红素酶异常反应的动力学
基本信息
- 批准号:10798604
- 负责人:
- 金额:$ 8.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-01 至 2027-08-31
- 项目状态:未结题
- 来源:
- 关键词:AnabolismAntibioticsBehaviorBiologicalBiotechnologyCell RespirationCommunicable DiseasesDevelopmentDiseaseEnzymesGoalsHealthHemeHumanHydroxylationImmune responseImmune systemLifeMedicineMetalsMethodologyMethodsOutcomePathway interactionsPharmacologic SubstanceProcessProductionReactionRegulationResearchRoleSignal TransductionSite-Directed MutagenesisSystemTherapeuticTimeVisualizationX-Ray Crystallographyanaloganti-cancer therapeuticbiochemical toolscancer therapycatalystcofactorcombatfascinatehormone biosynthesisinterestmetalloenzymenitrationstructural biology
项目摘要
ABSTRACT
Enzymes are crucial biological catalysts that expedite challenging reactions across all domains
of life. While the development of structural biology methods over the past century has enabled
visualization of these fascinating systems, our understanding of the dynamic processes that
facilitate enzyme reactivity remains limited due to the timescales on which they occur. The
overarching goal in my research group is to develop and apply time-resolved methods capable of
visualizing these processes to elucidate the mechanisms of metal-containing enzymes important
for human health and medicine. Heme-dependent enzymes are of particular interest due to their
role in aerobic metabolism ranging from signal transduction, antibiotic biosynthesis and immune
response. Despite sharing similar structural motifs and catalytic intermediates, heme-dependent
enzymes are capable of catalyzing a wide range of reactions beyond their archetypal
hydroxylation outcomes. This project aims to investigate the structural features and dynamic
behavior that enables this atypical reactivity from dioxygenation to nitration and beyond. In
particular, we plan to repurpose biochemical tools capable of pausing turnover, such as
substrate/cofactor analogs and site-directed mutagenesis, as well as apply state-of-the-art time-
resolved methods that my group is currently developing, to visualize short-lived catalytic
intermediates via a combination of X-ray crystallographic and spectroscopic approaches.
Although applied to specific systems herein, the proposed methodologies may have utility in the
study of heme-enzymes more broadly, as well as other metalloenzymes. Likewise, the anticipated
results have the potential to impact both biocatalysis and the downstream development of
biotechnologies and therapeutics in the treatment of cancers and infectious diseases.
摘要
酶是关键的生物催化剂,可以加速所有领域具有挑战性的反应。
生活的一部分。虽然结构生物学方法在过去一个世纪的发展使
这些引人入胜的系统的可视化,我们对动态过程的理解
由于它们发生的时间尺度,促进酶反应的活性仍然有限。这个
我的研究小组的首要目标是开发和应用时间分辨方法,能够
可视化这些过程以阐明含金属酶的机制很重要
为了人类的健康和医学。依赖于血红素的酶特别令人感兴趣,因为它们
在有氧代谢中的作用,包括信号转导、抗生素生物合成和免疫
回应。尽管有相似的结构基序和催化中间体,但依赖于血红素
酶能够催化超出其原型的一系列反应。
羟化结果。本项目旨在研究其结构特点和动态特性
使这种非典型的反应从双氧化到硝化甚至更远的行为。在……里面
特别是,我们计划重新使用能够暂停周转的生化工具,例如
底物/辅因子类似物和定点突变,以及应用最先进的时间-
我的团队目前正在开发的解决方法,以可视化短暂的催化
通过X射线结晶学和光谱学相结合的方法合成中间体。
虽然适用于本文中的特定系统,但建议的方法可能在
更广泛地研究血红素酶,以及其他金属酶。同样,预期的
结果有可能影响生物催化和下游的发展
治疗癌症和传染病的生物技术和治疗学。
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)
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Katherine Marie Davis其他文献
Katherine Marie Davis的其他文献
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{{ truncateString('Katherine Marie Davis', 18)}}的其他基金
Unraveling the dynamics that enable unusual heme enzyme reactivity
揭示血红素酶异常反应的动力学
- 批准号:
10501336 - 财政年份:2022
- 资助金额:
$ 8.5万 - 项目类别:
Unraveling the dynamics that enable unusual heme enzyme reactivity
揭示血红素酶异常反应的动力学
- 批准号:
10810351 - 财政年份:2022
- 资助金额:
$ 8.5万 - 项目类别:
Unraveling the dynamics that enable unusual heme enzyme reactivity
揭示血红素酶异常反应的动力学
- 批准号:
10670417 - 财政年份:2022
- 资助金额:
$ 8.5万 - 项目类别:
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