Crystal structures of UDP‐N‐acetylmuramic acid l‐alanine ligase (MurC) from Mycobacterium bovis with and without UDP‐N‐acetylglucosamine,Acta Crystallographica Section D

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Crystal structures of UDP‐N‐acetylmuramic acid l‐alanine ligase (MurC) from Mycobacterium bovis with and without UDP‐N‐acetylglucosamine
Acta Crystallographica Section D ( IF 2.6 ) Pub Date : 2021-05-05 , DOI: 10.1107/s2059798321002199
Pil Won Seo ₁ , Suk Youl Park ₂ , Andreas Hofmann ₃ , Jeong Sun Kim ₁

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Peptidoglycan comprises repeating units of N‐acetylmuramic acid, N‐acetylglucosamine and short cross‐linking peptides. After the conversion of UDP‐N‐acetylglucosamine (UNAG) to UDP‐N‐acetylmuramic acid (UNAM) by the MurA and MurB enzymes, an amino acid is added to UNAM by UDP‐N‐acetylmuramic acid l‐alanine ligase (MurC). As peptidoglycan is an essential component of the bacterial cell wall, the enzymes involved in its biosynthesis represent promising targets for the development of novel antibacterial drugs. Here, the crystal structure of Mycobacterium bovis MurC (MbMurC) is reported, which exhibits a three‐domain architecture for the binding of UNAM, ATP and an amino acid as substrates, with a nickel ion at the domain interface. The ATP‐binding loop adopts a conformation that is not seen in other MurCs. In the UNAG‐bound structure of MbMurC, the substrate mimic interacts with the UDP‐binding domain of MbMurC, which does not invoke rearrangement of the three domains. Interestingly, the glycine‐rich loop of the UDP‐binding domain of MbMurC interacts through hydrogen bonds with the glucose moiety of the ligand, but not with the pyrophosphate moiety. These findings suggest that UNAG analogs might serve as potential candidates for neutralizing the catalytic activity of bacterial MurC.

中文翻译：

来自牛分枝杆菌的 UDP-N-乙酰胞壁酸 l-丙氨酸连接酶 (MurC) 的晶体结构，有和没有 UDP-N-乙酰氨基葡萄糖

肽聚糖由N-乙酰胞壁酸、N-乙酰氨基葡萄糖和短交联肽的重复单元组成。UDP-的转换后Ñ乙酰氨基葡萄糖（UNAG），以UDP- Ñ由MURA和MurB酶-acetylmuramic酸（墨西哥国立自治大学），一个氨基酸由UDP-加入到墨西哥国立自治大学Ñ -acetylmuramic酸升丙氨酸连接酶（MURC） . 由于肽聚糖是细菌细胞壁的重要组成部分，参与其生物合成的酶代表了开发新型抗菌药物的有希望的目标。在这里，牛分枝杆菌MurC的晶体结构( Mb据报道，MurC) 具有三域结构，用于结合 UNAM、ATP 和氨基酸作为底物，在域界面处具有镍离子。ATP 结合环采用在其他 MurC 中未见的构象。在的UNAG绑定结构MB MURC，随着UDP结合结构域在基板模拟相互作用MB MURC，这不会调用三个结构域的重排。有趣的是，Mb MurC UDP 结合域的富含甘氨酸的环通过氢键与配体的葡萄糖部分相互作用，但不与焦磷酸部分相互作用。这些发现表明 UNAG 类似物可能作为中和细菌 MurC 催化活性的潜在候选物。

更新日期：2021-05-06

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