Molecular analysis of beta-lactamase structure and function
Molecular analysis of beta-lactamase structure and function
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DOI：
10.1078/1438-4221-00198
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发表时间：
2002-07-01
影响因子：
4.1
通讯作者：
Palzkill, TG
中科院分区：
文献类型：
--
作者：
Majiduddin, FK;Materon, IC;Palzkill, TG
在临床和农业环境中广泛且有时不负责任地使用β -内酰胺类抗生素，导致了耐药细菌的出现和广泛传播。细菌已经进化出三种策略来逃避β -内酰胺类抗生素的活性：1)改变靶点（如青霉素结合蛋白（PBPs））， 2)减少药物通过细菌膜的渗透（如外排泵）和3)产生β -内酰胺酶。β -内酰胺酶通过水解特征的四元β -内酰胺环的肽键使抗生素失效而使β -内酰胺抗生素失活。抗生素的失活提供了对细菌的抵抗力。目前，有超过300种β -内酰胺酶被描述，并进行了大量的动力学、结构、计算和诱变研究。在这篇综述中，我们讨论了最近对四种不同类型（A、B、C和D）的β -内酰胺酶的研究。这些研究进展进一步扩展了我们对这些复杂酶的认识，并有望为我们开发基于结构和合理设计的新抑制剂和抗生素提供额外的工具。
The extensive and sometimes irresponsible use of beta-lactam antibiotics in clinical and agricultural settings has contributed to the emergence and widespread dissemination of anti biotic-resistant bacteria. Bacteria have evolved three strategies to escape the activity of beta-lactam antibiotics: 1) alteration of the target site (e.g. penicillin-binding protein (PBPs), 2) reduction of drug permeation across the bacterial membrane (e.g. efflux pumps) and 3) production of beta-lactamase enzymes. The beta-lactamase enzymes inactivate beta-lactam antibiotics by hydrolyzing the peptide bond of the characteristic four-membered beta-lactam ring rendering the antibiotic ineffective. The inactivation of the antibiotic provides resistance to the bacterium. Currently, there are over 300 beta-lactamase enzymes described for which numerous kinetic, structural, computational and mutagenesis studies have been performed. In this review, we discuss the recent work performed on the four different classes (A, B, C, and D) of beta-lactamases. These investigative advances further expand our knowledge about these complex enzymes, and hopefully, will provide us with additional tools to develop new inhibitors and antibiotics based on structural and rational designs.