Bacterial Oxidases of the Cytochrome bd Family: Redox Enzymes of Unique Structure, Function, and Utility As Drug Targets
Bacterial Oxidases of the Cytochrome bd Family: Redox Enzymes of Unique Structure, Function, and Utility As Drug Targets
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DOI：
10.1089/ars.2020.8039
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发表时间：
2020-11-09
影响因子：
6.6
通讯作者：
Poole, Robert K.
中科院分区：
文献类型：
--
作者：
Borisov, Vitaliy B.;Siletsky, Sergey A.;Poole, Robert K.
意义：细胞色素BD是一种存在于许多原核生物呼吸链上的泛喹酚：氧氧化还原酶，具有独特的结构和功能特征。它的主要作用是将分子氧(即使在亚微摩尔浓度下)还原到水中，并产生用于生产三磷酸腺苷的质子动力。细胞色素BD在许多细菌病原体中都有发现，令人惊讶的是，在正式表示为厌氧菌的细菌中也发现了细胞色素BD。它赋予细菌对各种应激源的抵抗力，是一个潜在的药物靶点。最近的进展：我们从细胞色素BD的新的三维结构出发，综述了细胞色素BD的生化、结构和生理功能的最新进展。对新发现的细胞色素BD在帮助细菌抵御过氧化氢、一氧化氮、过氧亚硝酸盐和硫化氢的保护中的作用进行了评估。关键问题：关于这种多分子氧化酶中电子流动的精确描述以及如何实现对氧的极高亲和力，同时赋予细菌对其他小配体的抵抗力，仍然存在基本问题。未来方向：很明显，细胞色素BD在赋予细菌对有毒小分子的抗性方面具有独特的能力，这一特性对于理解病原体拥有这种氧化酶的倾向具有重要意义。由于细胞色素BD是一种独特的细菌酶，未来的研究应集中在利用其结构和功能的基础知识来开发新型有效的抗菌剂。
Significance: Cytochrome bd is a ubiquinol:oxygen oxidoreductase of many prokaryotic respiratory chains with a unique structure and functional characteristics. Its primary role is to couple the reduction of molecular oxygen, even at submicromolar concentrations, to water with the generation of a proton motive force used for adenosine triphosphate production. Cytochrome bd is found in many bacterial pathogens and, surprisingly, in bacteria formally denoted as anaerobes. It endows bacteria with resistance to various stressors and is a potential drug target.Recent Advances: We summarize recent advances in the biochemistry, structure, and physiological functions of cytochrome bd in the light of exciting new three-dimensional structures of the oxidase. The newly discovered roles of cytochrome bd in contributing to bacterial protection against hydrogen peroxide, nitric oxide, peroxynitrite, and hydrogen sulfide are assessed.Critical Issues: Fundamental questions remain regarding the precise delineation of electron flow within this multihaem oxidase and how the extraordinarily high affinity for oxygen is accomplished, while endowing bacteria with resistance to other small ligands.Future Directions: It is clear that cytochrome bd is unique in its ability to confer resistance to toxic small molecules, a property that is significant for understanding the propensity of pathogens to possess this oxidase. Since cytochrome bd is a uniquely bacterial enzyme, future research should focus on harnessing fundamental knowledge of its structure and function to the development of novel and effective antibacterial agents.