多磷酸激酶 2 (PPK2) 酶：结构、功能和在细菌生理学和毒力中的作用,International Journal of Molecular Sciences

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多磷酸激酶 2 (PPK2) 酶：结构、功能和在细菌生理学和毒力中的作用
International Journal of Molecular Sciences ( IF 4.9 ) Pub Date : 2022-01-10 , DOI: 10.3390/ijms23020670
Nolan Neville ₁ , Nathan Roberge ₁ , Zongchao Jia ₁

Affiliation

无机多磷酸盐 (polyP) 与一系列惊人的生物功能有关，从磷储存到分子伴侣活性再到细菌毒力。在细菌中，polyP 由多磷酸激酶 (PPK) 酶合成，该酶大致分为两个家族：PPK1 和 PPK2。虽然这两个酶家族都能够催化 polyP 的合成，但 PPK1 优先从核苷三磷酸合成 polyP，而 PPK2 优先消耗 polyP 以磷酸化核苷单磷酸或二磷酸。重要的是，许多致病菌如铜绿假单胞菌和鲍曼不动杆菌编码 PPK1 和 PPK2 中的至少一种，这表明这些酶可能是抗菌药物的有吸引力的靶标。尽管迄今为止大多数细菌息肉研究都集中在 PPK1，PPK2 酶也开始成为细菌生理学和下游毒力的重要调节剂。在这篇综述中，我们专门研究了 PPK2 对细菌息肉稳态的贡献。从对具有生化特征的 PPK2 的结构和功能的调查开始，我们总结了 PPK2 在细菌细胞中的作用，特别强调了毒力表型。此外，我们概述了开发抑制 PPK2 酶的药物的最新进展，并讨论了这种策略作为对抗细菌感染的新方法。从对生化特征 PPK2 的结构和功能的调查开始，我们总结了 PPK2 在细菌细胞中的作用，特别强调了毒力表型。此外，我们概述了开发抑制 PPK2 酶的药物的最新进展，并讨论了这种策略作为对抗细菌感染的新方法。从对生化特征 PPK2 的结构和功能的调查开始，我们总结了 PPK2 在细菌细胞中的作用，特别强调了毒力表型。此外，我们概述了开发抑制 PPK2 酶的药物的最新进展，并讨论了这种策略作为对抗细菌感染的新方法。

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Polyphosphate Kinase 2 (PPK2) Enzymes: Structure, Function, and Roles in Bacterial Physiology and Virulence

Inorganic polyphosphate (polyP) has been implicated in an astonishing array of biological functions, ranging from phosphorus storage to molecular chaperone activity to bacterial virulence. In bacteria, polyP is synthesized by polyphosphate kinase (PPK) enzymes, which are broadly subdivided into two families: PPK1 and PPK2. While both enzyme families are capable of catalyzing polyP synthesis, PPK1s preferentially synthesize polyP from nucleoside triphosphates, and PPK2s preferentially consume polyP to phosphorylate nucleoside mono- or diphosphates. Importantly, many pathogenic bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii encode at least one of each PPK1 and PPK2, suggesting these enzymes may be attractive targets for antibacterial drugs. Although the majority of bacterial polyP studies to date have focused on PPK1s, PPK2 enzymes have also begun to emerge as important regulators of bacterial physiology and downstream virulence. In this review, we specifically examine the contributions of PPK2s to bacterial polyP homeostasis. Beginning with a survey of the structures and functions of biochemically characterized PPK2s, we summarize the roles of PPK2s in the bacterial cell, with a particular emphasis on virulence phenotypes. Furthermore, we outline recent progress on developing drugs that inhibit PPK2 enzymes and discuss this strategy as a novel means of combatting bacterial infections.

更新日期：2022-01-10

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