Structures and Mechanisms of “Heme-oxygenase-like” Non-heme Di-iron Enzymes that Catalyze Complex N-oxygenation and Olefin-installing C–C-Fragmentation Reactions
催化复杂 N-氧化和烯烃安装 C-C 断裂反应的“类血红素加氧酶”非血红素双铁酶的结构和机制
基本信息
- 批准号:10647843
- 负责人:
- 金额:$ 32.86万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-07-10 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AccelerationActive SitesAffectAldehydesAlkenesAmazeAmino AcidsAntibioticsAntineoplastic AgentsAromatic AminesBackBindingBiochemicalBioinformaticsBiotechnologyBurn injuryCarbonChemicalsClinicalComplexCoupledDNA biosynthesisDataDedicationsDioxygenDirected Molecular EvolutionElectron TransportElectronsEnzymesEquilibriumExhibitsFamilyFerredoxinFerritinGoalsHemeHistidineHourHydrocarbonsIn SituIn VitroIndividualIonsIronIsomerismIsotopesKineticsKnowledgeLigandsMalignant neoplasm of pancreasMediatingMicrobeMixed Function OxygenasesNatural Product DrugNitroimidazolesOxidantsOxidasesOxidoreductaseOxygenasesPathway interactionsPharmaceutical PreparationsPlantsPlayProductionProteinsPublishingReactionRecyclingReducing AgentsReportingRoleScaffolding ProteinSiteSpectrum AnalysisStreptozocinStructureSystemTestingVariantWorkabsorptionabstractingadductcarboxylatecarboxylationcofactordesaturasedesignenzyme activityexpectationexperimental studyinsightmembermicrobialnoveloxidationscaffoldsmall molecule
项目摘要
Project Summary/Abstract
Enzymes that use coupled di-iron clusters that are coordinated by carboxylate and
histidine residues to activate dioxygen for difficult oxidation reactions play crucial roles in
the global carbon cycle, in DNA biosynthesis, and in synthesis of clinically used natural-
product drugs. In this last year, a new structural family of diiron enzymes has come into
focus. Related in structure to heme-oxygenase (HO), these HO-like diiron oxidase and
oxygenases (HODOs) have already expanded the known catalytic repertoire of the diiron
unit, even with only four members of the new family having been assigned biochemical
functions. In their functions, these HO-like enzymes produce antibiotics (the
nitroimidazoles), cancer drugs (streptozotocin), and jet fuel. Moreover, they appear to
function in a manner that is distinct from the functional paradigm that was established by
earlier work on other systems. Rather than remaining as stable cofactors within the HO-
proteins scaffolds, they spontaneously degrade, at least in vitro, perhaps as part of a
novel modus operandi that eliminates the requirement for cooperating proteins in their
catalytic cycles. The goal of this project is to understand the structures and mechanisms
of the first four functionally assigned members of what appears, on the basis of
bioinformatic analysis, to be a large and versatile new enzyme family. The expectation is
that an understanding of its functional principles might enable the new family to become a
privileged scaffold for directed evolution of new synthetically useful enzyme activities.
项目总结/摘要
使用偶联的二铁簇的酶,所述偶联的二铁簇由羧酸根和
组氨酸残基活化分子氧进行困难的氧化反应,
全球碳循环,DNA生物合成,以及临床使用的天然-
毒品产品。在过去的一年里,一个新的结构家族的二铁酶已经进入
专心点在结构上与血红素加氧酶(HO)相关,这些HO样二铁氧化酶和
加氧酶(霍多斯)已经扩展了已知的二铁催化库,
单位,即使只有四个成员的新家庭已被分配生化
功能协调发展的在它们的功能中,这些HO样酶产生抗生素(
硝基咪唑),抗癌药物(链脲霉素)和喷气燃料。此外,他们似乎
以一种不同于由以下方式建立的功能范式的方式发挥作用:
在其他系统上的早期工作。而不是作为HO内的稳定辅因子保持不变,
蛋白质支架,它们自发降解,至少在体外,也许作为一个
新的工作方式,消除了合作蛋白质的要求,
催化循环这个项目的目标是了解结构和机制
第一个四个功能分配的成员出现的基础上,
生物信息学分析,是一个大的和通用的新的酶家族。人们期望
理解家庭的功能性原则可能会使新家庭成为一个
用于定向进化新的合成有用的酶活性的特权支架。
项目成果
期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Structure and assembly of the diiron cofactor in the heme-oxygenase-like domain of the N-nitrosourea-producing enzyme SznF.
- DOI:10.1073/pnas.2015931118
- 发表时间:2021-01-26
- 期刊:
- 影响因子:11.1
- 作者:McBride MJ;Pope SR;Hu K;Okafor CD;Balskus EP;Bollinger JM Jr;Boal AK
- 通讯作者:Boal AK
Methods for Biophysical Characterization of SznF, a Member of the Heme-Oxygenase-Like Diiron Oxidase/Oxygenase Superfamily.
SznF(血红素加氧酶样二铁氧化酶/加氧酶超家族成员)的生物物理表征方法。
- DOI:10.1007/978-1-0716-3080-8_9
- 发表时间:2023
- 期刊:
- 影响因子:0
- 作者:McBride,MollyJ;Pope,SarahR;Nair,MrutyunjayA;Sil,Debangsu;Salas-Solá,XavierE;Krebs,Carsten;MartinBollingerJr,J;Boal,AmieK
- 通讯作者:Boal,AmieK
Synergistic Binding of the Halide and Cationic Prime Substrate of the l-Lysine 4-Chlorinase, BesD, in Both Ferrous and Ferryl States.
L-赖氨酸 4-氯酶 BesD 的卤化物和阳离子底物在亚铁和亚铁态下的协同结合。
- DOI:10.1101/2023.05.02.539147
- 发表时间:2023
- 期刊:
- 影响因子:0
- 作者:Slater,JeffreyW;Neugebauer,MonicaE;McBride,MollyJ;Sil,Debangsu;Lin,Chi-Yun;Katch,BryceJ;Boal,AmieK;Chang,MichelleCY;Silakov,Alexey;Krebs,Carsten;BollingerJr,JMartin
- 通讯作者:BollingerJr,JMartin
Substrate-Triggered μ-Peroxodiiron(III) Intermediate in the 4-Chloro-l-Lysine-Fragmenting Heme-Oxygenase-like Diiron Oxidase (HDO) BesC: Substrate Dissociation from, and C4 Targeting by, the Intermediate.
- DOI:10.1021/acs.biochem.1c00774
- 发表时间:2022-04-19
- 期刊:
- 影响因子:2.9
- 作者:McBride MJ;Nair MA;Sil D;Slater JW;Neugebauer ME;Chang MCY;Boal AK;Krebs C;Bollinger JM Jr
- 通讯作者:Bollinger JM Jr
Synergistic Binding of the Halide and Cationic Prime Substrate of l-Lysine 4-Chlorinase, BesD, in Both Ferrous and Ferryl States.
L-赖氨酸 4-氯酶 BesD 的卤化物和阳离子底物在亚铁和亚铁态下的协同结合。
- DOI:10.1021/acs.biochem.3c00248
- 发表时间:2023
- 期刊:
- 影响因子:2.9
- 作者:Slater,JeffreyW;Lin,Chi-Yun;Neugebauer,MonicaE;McBride,MollyJ;Sil,Debangsu;Nair,MrutyunjayA;Katch,BryceJ;Boal,AmieK;Chang,MichelleCY;Silakov,Alexey;Krebs,Carsten;BollingerJr,JMartin
- 通讯作者:BollingerJr,JMartin
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JOSEPH M BOLLINGER其他文献
JOSEPH M BOLLINGER的其他文献
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{{ truncateString('JOSEPH M BOLLINGER', 18)}}的其他基金
Structures and Mechanisms of “Heme-oxygenase-like” Non-heme Di-iron Enzymes that Catalyze Complex N-oxygenation and Olefin-installing C–C-Fragmentation Reactions
催化复杂 N-氧化和烯烃安装 C-C 断裂反应的“类血红素加氧酶”非血红素双铁酶的结构和机制
- 批准号:
10428624 - 财政年份:2020
- 资助金额:
$ 32.86万 - 项目类别:
Structures and Mechanisms of “Heme-oxygenase-like” Non-heme Di-iron Enzymes that Catalyze Complex N-oxygenation and Olefin-installing C–C-Fragmentation Reactions
催化复杂 N-氧化和烯烃安装 C-C 断裂反应的“类血红素加氧酶”非血红素双铁酶的结构和机制
- 批准号:
10035218 - 财政年份:2020
- 资助金额:
$ 32.86万 - 项目类别:
Structures and Mechanisms of “Heme-oxygenase-like” Non-heme Di-iron Enzymes that Catalyze Complex N-oxygenation and Olefin-installing C–C-Fragmentation Reactions
催化复杂 N-氧化和烯烃安装 C-C 断裂反应的“类血红素加氧酶”非血红素双铁酶的结构和机制
- 批准号:
10208910 - 财政年份:2020
- 资助金额:
$ 32.86万 - 项目类别:
Diverse Transition-Metal and Free-Radical Chemistry Enabling 2'-Deoxyribonucleotide Production by Bacteria in Restrictive Environments
多种过渡金属和自由基化学使细菌在限制性环境中生产 2-脱氧核糖核苷酸
- 批准号:
10165753 - 财政年份:2019
- 资助金额:
$ 32.86万 - 项目类别:
Diverse Transition-Metal and Free-Radical Chemistry Enabling 2'-Deoxyribonucleotide Production by Bacteria in Restrictive Environments
多种过渡金属和自由基化学使细菌在限制性环境中生产 2-脱氧核糖核苷酸
- 批准号:
10417125 - 财政年份:2019
- 资助金额:
$ 32.86万 - 项目类别:
Mechanisms and Reprogramming of Iron/2-Oxoglutarate Desaturases and Oxacyclases
铁/2-氧戊二酸去饱和酶和氧杂环酶的机制和重编程
- 批准号:
9262989 - 财政年份:2016
- 资助金额:
$ 32.86万 - 项目类别:
Mechanisms and Reprogramming of Iron/2-Oxoglutarate Desaturases and Oxacyclases
铁/2-氧戊二酸去饱和酶和氧杂环酶的机制和重编程
- 批准号:
9084003 - 财政年份:2016
- 资助金额:
$ 32.86万 - 项目类别:
Mechanisms of oxacycle- and olefin-installing iron/2-(oxo)glutarate oxygenases
安装氧杂环和烯烃的铁/2-(氧代)戊二酸加氧酶的机制
- 批准号:
9139962 - 财政年份:2015
- 资助金额:
$ 32.86万 - 项目类别:
Mechanisms of oxacycle- and olefin-installing iron/2-(oxo)glutarate oxygenases
安装氧杂环和烯烃的铁/2-(氧代)戊二酸加氧酶的机制
- 批准号:
8965103 - 财政年份:2015
- 资助金额:
$ 32.86万 - 项目类别:
Mechanisms of oxacycle- and olefin-installing iron/2-(oxo)glutarate oxygenases
安装氧杂环和烯烃的铁/2-(氧代)戊二酸加氧酶的机制
- 批准号:
9309007 - 财政年份:2015
- 资助金额:
$ 32.86万 - 项目类别:
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