Lee So Yeon, Park Hyun Ho
College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea.
Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Seoul 06974, Republic of Korea.
J Microbiol Biotechnol. 2025 Aug 26;35:e2505019. doi: 10.4014/jmb.2505.05019.
N-acetylglucosamine-6-phosphate deacetylase (NagA) is a conserved enzyme involved in bacterial amino sugar metabolism, catalyzing the conversion of GlcNAc-6-phosphate to GlcN-6-phosphate and acetate. While NagA typically function as dimers, its quaternary diversity across species remains underexplored. Here, we present the crystal structure of (kpNagA), which forms a homotetrameric assembly both in crystal and in solution, as confirmed by SEC-MALS. Each monomer adopts a canonical (β/α) TIM barrel fold with a β-sandwich subdomain, and its active site, located around β10-β11 and α3-α4, coordinates a divalent zinc ion. Comparative analyses revealed conserved dimer interfaces but divergent tetrameric arrangements. Notably, NagA also forms a stable tetramer, albeit via a distinct interface. These findings suggest species-specific tetramerization and broaden our understanding of NagA structural diversity and potential antibiotic targets.
N-乙酰葡糖胺-6-磷酸脱乙酰酶（NagA）是一种参与细菌氨基糖代谢的保守酶，催化6-磷酸葡糖胺（GlcN-6-P）转化为6-磷酸葡糖胺（GlcN-6-P）和乙酸盐。虽然NagA通常以二聚体形式发挥作用，但其在不同物种间的四级结构多样性仍未得到充分探索。在此，我们展示了肺炎克雷伯菌NagA（kpNagA）的晶体结构，经尺寸排阻色谱-多角度激光散射（SEC-MALS）证实，其在晶体和溶液中均形成同四聚体组装。每个单体采用具有β-三明治亚结构域的典型（β/α）TIM桶状折叠，其活性位点位于β10-β11和α3-α4附近，与一个二价锌离子配位。比较分析揭示了保守的二聚体界面，但四聚体排列不同。值得注意的是，嗜肺军团菌NagA也形成稳定的四聚体，尽管是通过不同的界面。这些发现表明了物种特异性的四聚化，并拓宽了我们对NagA结构多样性和潜在抗生素靶点的理解。
