Chakrabarty Arindam, Dutta Debajyoti, Baidya Mithu, Dutta Anirudha, Das Amit Kumar, Ghosh Sudip K
Department of Bioscience and Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.
Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala 147004, India.
Pathogens. 2025 Mar 13;14(3):277. doi: 10.3390/pathogens14030277.
Metronidazole is the preferred drug for treating amoebiasis caused by . Its antiamoebic activity is primarily attributed to activation by various reductases. This study reports an alternative activation pathway in mediated by the decarboxylating malic enzyme. Functional characterization of this NADPH-dependent enzyme reveals that it is secreted into the extracellular milieu and may play a role in adhesion to human enteric cells. Structural analysis of the malic enzyme (EhME) demonstrates that the protein forms a strict dimer, with the protomers interlocked by a unique knot structure formed by two polypeptide chains. This distinctive structural feature closely aligns EhME with its prokaryotic counterparts. In conclusion, our findings reveal that harbors a deeply entangled dimeric malic enzyme that contributes to metronidazole susceptibility, sharing structural similarities with bacterial malic enzymes.
甲硝唑是治疗由[具体病原体]引起的阿米巴病的首选药物。其抗阿米巴活性主要归因于各种还原酶的激活作用。本研究报道了由脱羧苹果酸酶介导的[病原体名称]中的另一种激活途径。对这种依赖NADPH的酶的功能表征表明，它被分泌到细胞外环境中，可能在[病原体名称]与人肠道细胞的黏附中起作用。对[病原体名称]苹果酸酶（EhME）的结构分析表明，该蛋白形成一个严格的二聚体，原体由两条多肽链形成的独特结结构相互锁定。这种独特的结构特征使EhME与其原核对应物紧密对齐。总之，我们的研究结果表明，[病原体名称]含有一种深度缠绕的二聚体苹果酸酶，它有助于甲硝唑的敏感性，与细菌苹果酸酶具有结构相似性。
