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Natural Engineering of Multi-Electron Biological Oxidation & Reduction

多电子生物氧化自然工程

基本信息

批准号：
8586267
负责人：
PETER LESLIE DUTTON
金额：
$ 40万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-02-01 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8586267
关键词：
Achievement Address Agriculture Biological Biology Breathing Catalysis Cell Respiration Characteristics Charge Chemicals Clinical Complex Development Devices Disease Ecology Electrodes Electron Transport Electrons Elements Engineering Environment Enzymes Equilibrium Failure Family Flavins Freedom Generations Geometry Goals Grant Guidelines Health Heme Heme Iron Hemoglobin Human In Vitro Intervention Knowledge Laboratories Laboratory Study Learning Life Light Medical Membrane Metals Motion NADPH Oxidase Natural Selections Nature Niacinamide Oxidants Oxidation-Reduction Oxidoreductase Oxygen Phase Physiological Plastocyanin Play Porphyrins Positioning Attribute Property Protein Binding Proteins Protons Pterins Quinones Reducing Agents Reproduction Research Respiration Role Semiconductors Site Solar Energy Stress Structure Sulfur Superoxides System Technology Titania Titanium Uncertainty Water Work aqueous catalyst chlorin cofactor cytochrome c design in vivo insight man member millisecond nanometer nanoscale operation oxidative damage public health relevance

项目摘要

DESCRIPTION (provided by applicant): The oxidoreductase superfamily is responsible for a very broad range of oxidative and reductive chemical transformations and energy conversions throughout biology. Many key members align cofactors such as chlorins, hemes, iron-sulfur clusters, flavins, quinones and metals to form single-electron-transfer chains through protein over multi-nanometer distances. At their termini, electrons exchange with sites of diffusible one-electron carriers (e. g. cytochrome c, plastocyanin) or sites of two-electron (flavin, quinone and nicotinamide) or four-electron (oxygen) oxidative and reductive catalysis. With the common catalytic features and a shared electron-tunneling engineering understood to a useful practical level, we have learned how to reproduce selected natural oxidoreductases functions by practical assembly in completely artificial proteins built from scratch. We are now poised to assemble the components into extended single-electron-transfer chains, to construct operating two-electron catalytic termini akin to those seen in Nature, and to functionally connect these chains and termini. We exploit the simplicity and adaptability of these artificial proteins we call maquettes, and their freedom from the obscuring complexity and fragility of natural proteins. The maquettes form a type of laboratory to uncover new insights into oxidative metabolism and energy conversion during normal operation of natural electron-transfer systems in respiration, into the vulnerabilities to oxidative damage during physiological operation and into their failure under conditions of stress or disease. We also aim to bridge the gap between hopeful bio-inspiration and the reality of practical reproduction of the remarkable catalytic capability of natural oxidoreductases in settings that can be put to work for human needs.

描述（由申请人提供）：氧化还原酶超家族负责整个生物学中非常广泛的氧化和还原化学转化以及能量转化。许多关键成员排列辅因子，如二氢卟酚，血红素，铁硫簇，黄素，醌和金属，形成单电子转移链，通过蛋白质在多纳米的距离。在它们的末端，电子与可扩散的单电子载流子的位点交换（例如，电子交换）。G.细胞色素c、质体蓝素）或二电子（黄素、醌和烟酰胺）或四电子（氧）氧化和还原催化的位点。随着共同的催化功能和共享的电子隧道工程理解到一个有用的实用水平，我们已经学会了如何复制选择的天然氧化还原酶功能的实际组装在完全人工蛋白质从头开始。我们现在准备组装成扩展的单电子转移链的组件，构建类似于自然界中看到的操作双电子催化末端，并在功能上连接这些链和末端。我们利用这些我们称之为maquettes的人工蛋白质的简单性和适应性，以及它们从天然蛋白质的模糊复杂性和脆弱性中的自由。这些模型形成了一种实验室，揭示了呼吸中天然电子转移系统正常运行期间氧化代谢和能量转换的新见解，以及生理操作期间氧化损伤的脆弱性以及在压力或疾病条件下的失败。我们还旨在弥合希望的生物灵感与实际再现天然氧化还原酶在可用于满足人类需求的环境中的显着催化能力之间的差距。

项目成果

期刊论文数量（28）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Tailorable Tetrahelical Bundles as a Toolkit for Redox Studies.

DOI：
10.1021/acs.jpcb.2c05119
发表时间：
2022-10-20
期刊：
JOURNAL OF PHYSICAL CHEMISTRY B
影响因子：
3.3
作者：
Solomon, Lee A.;Witten, Joshua;Kodali, Goutham;Moser, Christopher C.;Dutton, P. Leslie
通讯作者：
Dutton, P. Leslie

Design and engineering of an O(2) transport protein.

O（2）转运蛋白的设计和工程。

DOI：
10.1038/nature07841
发表时间：
2009-03-19
期刊：
NATURE
影响因子：
64.8
作者：
Koder, Ronald L.;Anderson, J. L. Ross;Solomon, Lee A.;Reddy, Konda S.;Moser, Christopher C.;Dutton, P. Leslie
通讯作者：
Dutton, P. Leslie

An electronic bus bar lies in the core of cytochrome bc1.