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金属β-内酰胺酶:结构特征、抗生素识别、抑制和抑制剂设计。

Metallo-β-lactamases: structural features, antibiotic recognition, inhibition, and inhibitor design.

机构信息

Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.

出版信息

Curr Top Med Chem. 2013;13(10):1242-53. doi: 10.2174/15680266113139990011.

Abstract

Owing to their ability in destroying or slowing down the growth of bacteria, antibiotics have been widely used to treat the bacterial infections. However, because of the long-term and irresponsible use of antibiotics, resistance to antibiotics has become a serious problem directly threatening the public health worldwide. To fight against and resist β- lactam antibiotics, bacteria usually employed β-lactamases, especially the metallo-β-lactamases, to hydrolyze the C-N bond of the β-lactam ring so as to inactivate the antibiotics. In this minireview, we are to summarize the structural features of the metallo-β-lactamases, as well as their antibiotic binding modes and resistance mechanisms, in hopes that the discussion and analysis presented in this paper can stimulate new strategies to overcome the resistance problem and find novel inhibitors against the metallo-β-lactamases.

摘要

由于抗生素具有破坏或减缓细菌生长的能力,因此被广泛用于治疗细菌感染。然而,由于抗生素的长期和不负责任的使用,抗生素耐药性已成为直接威胁全球公众健康的严重问题。为了对抗和抵抗β-内酰胺类抗生素,细菌通常会使用β-内酰胺酶,特别是金属β-内酰胺酶,来水解β-内酰胺环的 C-N 键,从而使抗生素失活。在这篇综述中,我们将总结金属β-内酰胺酶的结构特征,以及它们与抗生素的结合模式和耐药机制,希望本文的讨论和分析能够激发克服耐药性问题的新策略,并找到针对金属β-内酰胺酶的新型抑制剂。

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