Dynamics of Electron and Proton Transfer Chemistry in Copper and Hybrid Copper-Haem Enzymes

铜和杂化铜血红素酶中电子和质子转移化学的动力学

• 批准号: BB/M020924/1
• 负责人: Richard Strange
• 金额: $ 33.28万
• 依托单位: University of Essex
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM020924%2F1
• 关键词: Dynamics; Electron; Proton; Transfer; Chemistry

The mechanisms of effective electron and proton transfer in chemical processes, to catalyse chemical reactions and enable essential biochemical functions, are still not fully understood. This proposal combines state of the art experimental and high performance computational methods to address these questions, developing innovative approaches with a focus on proteins that perform fundamental chemistry that is important to the environment as part of the global nitrogen cycle. New experimental methods include rapid room temperature X-ray crystallography and single crystal spectroscopies, while the theoretical approach will be a mixture of quantum mechanics, molecular mechanics and molecular dynamics, with the calculations performed on state of the art parallel processing computer systems.Copper nitrite reductases are important environmental proteins that carry out the chemistry to convert nitrite (NO2) to nitric oxide (NO) during the process of denitrification, a key step of the biological 'nitrogen cycle' whereby nitrogen gas is returned from the soil to the atmosphere. We will first study this process in an enzyme from Achromobacter cycloclastes. It requires binding of NO2 to a Cu atom and its reduction to NO via mechanisms involving a second Cu atom and electron and proton transfer to the 'active site'. This also normally involves the formation of a normally transient complex between the nitrite reductase and a cytochrome (electron donor) partner protein, making the chemistry difficult to study. Recently a new nitrite reductase has been discovered that contains a 'tethered' cytochrome domain. This protein, from Ralstonia picketti, acts as a 'self-contained electron transfer' system, an unusual and rare structure that negates the need for a transient protein-protein complex and which provides us with the unique opportunity to fully study such a fundamental catalytic process in detail, ie electron transfer, proton transfer, NO2 delivery and binding, as well as the metal oxidation states.The outcomes of our programme will be of broad relevance to any chemistry involving controlled electron and proton transfer reactions, processes that are ubiquitous in nature, and essential for future development of efficient biomimetic compounds or synthetic enzymes & enzyme-inspired catalysts for industrial applications.

化学过程中有效的电子和质子转移、催化化学反应和实现基本生化功能的机制尚未完全了解。该提案结合了最先进的实验和高性能计算方法来解决这些问题，开发创新方法，重点关注执行基本化学的蛋白质，作为全球氮循环的一部分，这对环境很重要。新的实验方法包括快速室温 X 射线晶体学和单晶光谱学，而理论方法将是量子力学、分子力学和分子动力学的混合，并在最先进的并行处理计算机系统上进行计算。亚硝酸铜还原酶是重要的环境蛋白质，在亚硝酸盐 (NO2) 转化为一氧化氮 (NO) 的过程中进行化学反应。 反硝化是生物“氮循环”的关键步骤，氮气从土壤返回到大气中。我们将首先在环碎无色杆菌的酶中研究这一过程。它需要将 NO2 与 Cu 原子结合，并通过涉及第二个 Cu 原子以及电子和质子转移到“活性位点”的机制将其还原为 NO。这通常还涉及亚硝酸还原酶和细胞色素（电子供体）伴侣蛋白之间通常短暂的复合物的形成，使得化学难以研究。最近发现了一种新的亚硝酸还原酶，它含有“束缚”细胞色素结构域。这种来自 Ralstonia picketti 的蛋白质充当“独立电子转移”系统，这是一种不寻常且罕见的结构，不需要瞬时蛋白质-蛋白质复合物，并为我们提供了独特的机会来详细研究这种基本催化过程，即电子转移、质子转移、NO2 传递和结合以及金属氧化态。我们计划的结果将与任何化学具有广泛的相关性 涉及受控的电子和质子转移反应，这些过程在自然界中普遍存在，对于未来开发用于工业应用的高效仿生化合物或合成酶和酶启发催化剂至关重要。

项目成果

A QM/MM Study of Nitrite Binding Modes in a Three-Domain Heme-Cu Nitrite Reductase.

• DOI: 10.3390/molecules23112997
• 发表时间: 2018-11-16
• 期刊: Molecules (Basel, Switzerland)
• 作者: Sen K;Hough MA;Strange RW;Yong CW;Keal TW
• 通讯作者: Keal TW

Photoreduction and validation of haem-ligand intermediate states in protein crystals by in situ single-crystal spectroscopy and diffraction.

• DOI: 10.1107/s2052252517002159
• 发表时间: 2017-05-01
• 期刊: IUCrJ
• 影响因子: 3.9
• 作者: Kekilli D;Moreno-Chicano T;Chaplin AK;Horrell S;Dworkowski FSN;Worrall JAR;Strange RW;Hough MA
• 通讯作者: Hough MA

Nature of the copper-nitrosyl intermediates of copper nitrite reductases during catalysis.

• DOI: 10.1039/d0sc04797j
• 发表时间: 2020-10-20
• 期刊: Chemical science
• 影响因子: 8.4
• 作者: Hough MA;Conradie J;Strange RW;Antonyuk SV;Eady RR;Ghosh A;Hasnain SS
• 通讯作者: Hasnain SS

Enzyme catalysis captured using multiple structures from one crystal at varying temperatures.

• DOI: 10.1107/s205225251800386x
• 发表时间: 2018-05-01
• 期刊: IUCrJ
• 影响因子: 3.9
• 作者: Horrell S;Kekilli D;Sen K;Owen RL;Dworkowski FSN;Antonyuk SV;Keal TW;Yong CW;Eady RR;Hasnain SS;Strange RW;Hough MA
• 通讯作者: Hough MA

Distinguishing Nitro vs Nitrito Coordination in Cytochrome c' Using Vibrational Spectroscopy and Density Functional Theory.

• DOI: 10.1021/acs.inorgchem.7b01945
• 发表时间: 2017-11-06
• 期刊: Inorganic chemistry
• 影响因子: 4.6
• 作者: Nilsson ZN;Mandella BL;Sen K;Kekilli D;Hough MA;Moënne-Loccoz P;Strange RW;Andrew CR
• 通讯作者: Andrew CR