Class B beta-lactamases or metallo-beta-lactamases (MBLs) require zinc ions to catalyse the hydrolysis of beta-lactam antibiotics such as penicillins, cephalosporins, carbapenems, and cephamycins. There are no clinically useful inhibitors against MBLs which are responsible for the resistance of some bacteria to antibiotics. There are two metal-ion binding sites that have different zinc ligands but the exact roles of the metal-ion remain controversial, and distinguishing between their relative importance is complex. The metal-ion can act as a Lewis acid by co-ordination to the beta-lactam carbonyl oxygen to facilitate nucleophilic attack and stabilise the negative charge developed on this oxygen in the tetrahedral intermediate anion. The metal-ion also lowers the pKa of the directly co-ordinated water molecule so that the metal-bound hydroxide ion is a better nucleophile than water and is used to attack the beta-lactam carbonyl carbon. An intrinsic property of binuclear metallo hydrolytic enzymes that depend on a metal-bound water both as the attacking nucleophile and as a ligand for the second metal-ion is that this water molecule, which is consumed during hydrolysis of the substrate, has to be replaced to maintain the catalytic cycle. With MBL this is reflected in some unusual kinetic profiles.

中文翻译：

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金属β-内酰胺酶的催化机制。

B 类 β-内酰胺酶或金属-β-内酰胺酶 (MBL) 需要锌离子来催化 β-内酰胺抗生素（如青霉素、头孢菌素、碳青霉烯类和头霉素）的水解。没有临床上有用的 MBL 抑制剂，MBL 是导致某些细菌对抗生素产生抗性的原因。有两个金属离子结合位点具有不同的锌配体，但金属离子的确切作用仍然存在争议，区分它们的相对重要性很复杂。金属离子可以通过与 β-内酰胺羰基氧配位来充当路易斯酸，以促进亲核攻击并稳定四面体中间阴离子中在该氧上产生的负电荷。金属离子还降低了直接配位的水分子的 pKa，因此与金属结合的氢氧根离子是比水更好的亲核试剂，用于攻击 β-内酰胺羰基碳。双核金属水解酶依赖金属结合水作为攻击亲核试剂和第二个金属离子的配体，其固有特性是在底物水解过程中消耗的水分子必须被替换以维持催化循环。对于 MBL，这反映在一些不寻常的动力学曲线中。双核金属水解酶依赖于金属结合水作为攻击亲核试剂和第二个金属离子的配体，其固有特性是在底物水解过程中消耗的这种水分子必须被替换以维持催化循环。对于 MBL，这反映在一些不寻常的动力学曲线中。双核金属水解酶依赖于金属结合水作为攻击亲核试剂和第二金属离子的配体，其固有特性是在底物水解过程中消耗的这种水分子必须被替换以维持催化循环。对于 MBL，这反映在一些不寻常的动力学曲线中。