Chen Xinglan, Gou Lingzhu, Wang Yuanyuan, Yang Jinxia, Dong Yeze, Xie Baoyuan, Zhang Dekui
Key Laboratory of Digestive Diseases of Gansu Province, The Second Hospital of Lanzhou University, Lanzhou, 730030, People's Republic of China.
Infect Drug Resist. 2025 Jun 17;18:3037-3053. doi: 10.2147/IDR.S519194. eCollection 2025.
infection is closely linked to digestive diseases such as inflammation, ulceration, gastric cancer, and mucosa-associated lymphoid tissue lymphoma. Current treatment relies on antibiotic combinations, but antibiotic resistance increasingly undermines eradication efforts. Urease, a metalloenzyme secreted by , is crucial for bacterial colonization. Traditional urease inhibitors target either the active site or mimic the substrate, but the buried active site poses a challenge for effective inhibition. Moreover, current inhibitors often have non-negligible side effects. Recent research highlights complex interactions during urease maturation, involving auxiliary proteins and nickel ion transfer. These studies suggest that auxiliary proteins involved in metalloenzyme maturation, as well as the process of nickel ion delivery, could be novel targets for inhibitors. This review summarizes nickel ion delivery during urease maturation, interactions between auxiliary proteins, and the structure of the active site. It also categorizes and summarizes half inhibitory concentration (IC) values of existing inhibitors. Finally, we discuss potential inhibitors'mechanisms of action, challenges, and future perspectives, aiming to provide new strategies for eradicating infection.
感染与消化系统疾病密切相关，如炎症、溃疡、胃癌和黏膜相关淋巴组织淋巴瘤。目前的治疗依赖于联合使用抗生素，但抗生素耐药性日益削弱根除感染的努力。脲酶是由[细菌名称未给出]分泌的一种金属酶，对细菌定植至关重要。传统的脲酶抑制剂要么靶向活性位点，要么模拟底物，但深埋的活性位点对有效抑制构成挑战。此外，目前的抑制剂往往有不可忽视的副作用。最近的研究突出了脲酶成熟过程中的复杂相互作用，涉及辅助蛋白和镍离子转移。这些研究表明，参与金属酶成熟的辅助蛋白以及镍离子传递过程可能是抑制剂的新靶点。本综述总结了脲酶成熟过程中的镍离子传递、辅助蛋白之间的相互作用以及活性位点的结构。它还对现有抑制剂的半数抑制浓度（IC）值进行了分类和总结。最后，我们讨论了潜在抑制剂的作用机制、挑战和未来前景，旨在为根除[感染源未明确给出]感染提供新策略。
