Resistance to β-lactams is one of the most serious problems associated with Gram-negative infections. β-Lactamases are able to hydrolyze β-lactams such as cephalosporins and/or carbapenems. Evolutionary origin of metallo-β-lactamases (MBLs), conferring critical antibiotic resistance threats, remains unknown. We discovered PNGM-1, the novel subclass B3 MBL, in deep-sea sediments that predate the antibiotic era. Here, our phylogenetic analysis suggests that PNGM-1 yields insights into the evolutionary origin of subclass B3 MBLs. We reveal the structural similarities between tRNase Zs and PNGM-1, and demonstrate that PNGM-1 has both MBL and tRNase Z activities, suggesting that PNGM-1 is thought to have evolved from a tRNase Z. We also show kinetic and structural comparisons between PNGM-1 and other proteins including subclass B3 MBLs and tRNase Zs. These comparisons revealed that the B3 MBL activity of PNGM-1 is a promiscuous activity and subclass B3 MBLs are thought to have evolved through PNGM-1 activity.

中文翻译：

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PNGM-1的双重活性指出了B3类金属β-内酰胺酶的进化起源：一项分子和进化研究。

对β-内酰胺类的耐药性是与革兰氏阴性感染相关的最严重的问题之一。β-内酰胺酶能够水解β-内酰胺，例如头孢菌素和/或碳青霉烯。金属-β-内酰胺酶（MBL）的进化起源，赋予关键的抗生素耐药性威胁，仍然是未知的。我们在抗生素时代之前的深海沉积物中发现了新的B3 MBL亚类PNGM-1。在这里，我们的系统发育分析表明，PNGM-1可以深入了解B3 MBL亚类的进化起源。我们揭示了tRNase Zs和PNGM-1之间的结构相似性，并证明PNGM-1同时具有MBL和tRNase Z活性，这表明PNGM-1被认为是从tRNase Z进化而来的。我们还显示了之间的动力学和结构比较PNGM-1和其他蛋白质，包括亚类B3 MBL和tRNaseZ。