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Outline
Metallo-β-lactamases (MBLs) mediate carbapenem antibiotic resistance by hydrolyzing the β-lactam ring. However, existing inhibitors remain largely confined to laboratory research due to poor selectivity or insufficient potency, and no clinically approved MBL inhibitors are currently available. MBLs are categorized into three subclasses B1, B2, and B3. B1 and B3 subclasses possess a binuclear zinc catalytic center, whereas B2 harbors a single active zinc ion. Despite their structurally conserved active sites featuring a characteristic αβ/βα-fold architecture with catalytic zinc ions positioned between αβ units flanked by flexible loops. Meanwhile, candidates developed through enzymatic and thermodynamic studies, such as 2-quinazolinone QDP-1, boronic acid derivatives VNRX-5133/QPX7728, thiazolecarboxylic acid ANT2681, and selenium-containing compound SPI-1005, still face challenges in achieving broad-spectrum efficacy and clinical safety. This review systematically examines the interaction mechanisms between inhibitors and MBLs, focusing on three strategic approaches: Covalent binding strategies, zinc ion chelation, and allosteric inhibition. The synthesis aims to provide theoretical foundations and rational design strategies for developing potent, safe, and broad-spectrum metallo-β-lactamase inhibitors.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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