Department of Computational Biology & Bioinformatics, Sam Higginbottom University of Agriculture, Technology and Sciences, Allahabad 211007, U.P., India.
Department of Dermatology, University of Michigan Medical School, Ann arbor, MI 48109, USA.
Infect Genet Evol. 2019 Jan;67:101-111. doi: 10.1016/j.meegid.2018.11.001. Epub 2018 Nov 2.
Ornithine decarboxylase (ODC) is an immediate precursor of polyamine biosynthesis in Serratia marcescens and a potential target for inhibition of its growth. We predicted the 3D structural conformation of ODC enzyme and validated it using MDS in our previous study. In this current study, the potential inhibitors of ODC were obtained by virtual screening of potential inhibitors from ZINC database and studied in depth for their different binding pose. Among the ten virtually screened inhibitors, Conessine exhibited the best binding with ODC and its inhibition property was studied further by MDS studies. The natural compound conessine is isolated from plant Holarrhena antidysenterica and it is studied against ODC of Serratia marcenses for its inhibitory potentials. This revealed unforeseen twisted position in root mean square fluctuation (RMSF) and ODC modelled conformation that influenced ligand binding. Both predicted model and ligand bound model were compared and found to be stable with Root Mean Square Deviation (RMSD) of approximately 7 nm and 0.25 nm to that of crystallographic structure over simulation time of 55 ns and 70 ns respectively. This work paves the way for future development of new drugs against nosocomial diseases caused by Serratia marcescens.
鸟氨酸脱羧酶（ODC）是粘质沙雷氏菌多胺生物合成的直接前体，也是抑制其生长的潜在靶点。在我们之前的研究中，我们预测了 ODC 酶的 3D 结构构象，并使用 MDS 对其进行了验证。在本研究中，通过从 ZINC 数据库中虚拟筛选潜在抑制剂，获得了 ODC 的潜在抑制剂，并深入研究了它们的不同结合构象。在十种虚拟筛选的抑制剂中，康内辛与 ODC 的结合效果最好，并进一步通过 MDS 研究研究了其抑制特性。天然化合物康内辛从植物 Holarrhena antidysenterica 中分离出来，研究其对粘质沙雷氏菌 ODC 的抑制潜力。这揭示了均方根波动（RMSF）和 ODC 建模构象中未预料到的扭曲位置，这影响了配体结合。预测模型和配体结合模型都进行了比较，发现它们在模拟时间为 55ns 和 70ns 时，与晶体结构的 RMSD 分别约为 7nm 和 0.25nm，均具有稳定性。这项工作为未来开发针对粘质沙雷氏菌引起的医院获得性疾病的新药铺平了道路。
