Many of the pathogenic microbes use trehalose–6–phosphate phosphatase (TPP) enzymes for biosynthesis of sugar trehalose from trehalose–6–phosphate (T6P) in their pathway of infection and proliferation. Therefore, the present work is an approach to design new generation candidate drugs to inhibit TPP through in silico methods. Blast P and Clustal Omega phylogenetic analysis of TPP sequences were done for 12 organisms that indicate and confirm the presence of three conserved active site regions of known TPPs. Docking studies of 3D model of TPP with 17 phytochemicals revealed most of them have good binding affinity to an enzyme with rutin exhibiting highest affinity (Binding energy of − 7 kcal/mole). It has been found that during docking, phytochemical leads bind to active site region 3 of TPP sequences which coordinates Mg2+ and essential for catalysis. Binding poses and distance measurement of TPP-phytochemical complexes of rutin, carpaine, stigmasterol, β-caryophyllene, and α-eudesmol reveals that the lead phytochemicals were in close proximity with most of the active site amino acids of region 3 (distance range from 1.796 to 2.747 Ao). This confirms the tight binding between enzyme and leads which may pave way for the discovery of new generation drugs against TPP producing pathogenic microbes to manage diseases.

中文翻译：

---

植物化学物质对病原微生物海藻糖-6-磷酸磷酸酶的分子对接研究

许多病原微生物在其感染和增殖途径中使用 6-磷酸海藻糖磷酸酶 (TPP) 酶从 6-磷酸海藻糖 (T6P) 生物合成海藻糖。因此，目前的工作是一种通过计算机方法设计新一代候选药物以抑制 TPP 的方法。对 12 种生物进行了 TPP 序列的 Blast P 和 Clustal Omega 系统发育分析，表明并确认了已知 TPP 的三个保守活性位点区域的存在。TPP 的 3D 模型与 17 种植物化学物质的对接研究表明，它们中的大多数对芦丁具有最高亲和力的酶具有良好的结合亲和力（结合能为 - 7 kcal/mole）。已经发现，在对接过程中，植物化学先导物与 TPP 序列的活性位点区域 3 结合，该区域协调 Mg2+ 并对催化至关重要。芦丁、卡巴因、豆甾醇、β-石竹烯和α-丁香酚的 TPP-植物化学复合物的结合姿势和距离测量表明，主要植物化学物质与区域 3 的大多数活性位点氨基酸非常接近（距离范围从 1.796到 2.747 Ao)。这证实了酶和先导物之间的紧密结合，这可能为发现针对产生 TPP 的病原微生物以控制疾病的新一代药物铺平道路。α-eudesmol 表明铅植物化学物质与区域 3 的大多数活性位点氨基酸非常接近（距离范围从 1.796 到 2.747 Ao）。这证实了酶和先导物之间的紧密结合，这可能为发现针对产生 TPP 的病原微生物以控制疾病的新一代药物铺平道路。α-eudesmol 表明铅植物化学物质与区域 3 的大多数活性位点氨基酸非常接近（距离范围从 1.796 到 2.747 Ao）。这证实了酶和先导物之间的紧密结合，这可能为发现针对产生 TPP 的病原微生物以控制疾病的新一代药物铺平道路。