Identification of fungus-growing termite-associated halogenated-PKS maduralactomycin a as a potential inhibitor of MurF protein of multidrug-resistant Acinetobacter baumannii.
Identification of fungus-growing termite-associated halogenated-PKS maduralactomycin a as a potential inhibitor of MurF protein of multidrug-resistant Acinetobacter baumannii.
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DOI：
10.3389/fmolb.2023.1183073
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发表时间：
2023
影响因子：
5
通讯作者：
中科院分区：
文献类型：
--
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多重耐药鲍曼不动杆菌感染已成为全球主要的公共卫生问题。抑制其必需的MurF蛋白已被提议作为广谱药物的潜在靶点。本研究的目的是评估一个新的生态位的潜力374真菌生长的白蚁相关的天然产物（NP）。分子对接和计算药代动力学筛选了四个化合物，Termstrin B、Fridamycin A、Maduralactomycin A和Natalenamide C，作为具有较高结合亲和力和有利的蛋白质-配体相互作用的潜在化合物。化合物马杜拉乳霉素A基于其最低的平均RMSD值（2.31 μ m）和低标准偏差（0.35）诱导了更高的稳定性，这是由蛋白质的时间依赖性运动期间的一致柔性和β因子支持的。虽然氢键分析表明Termstrin B形成了最强的蛋白质内相互作用，但溶剂可及性与马杜拉乳霉素A紧密性良好一致。在所有化合物中，马杜拉乳霉素A的结合能最强（−348.48 kcal/mol），其次是Termstrin B（−321.19 kcal/mol）。由于这些发现表明马杜拉菌素A和Termstrin B是抑制MurF蛋白的有希望的候选物，因此马杜拉菌素A的有利结合能使其成为更重要的化合物，值得进一步研究。然而，在得出任何最终结论之前，建议使用动物模型和临床试验进行实验验证。
Multidrug-resistant Acinetobacter baumannii infections have become a major public health concern globally. Inhibition of its essential MurF protein has been proposed as a potential target for broad-spectrum drugs. This study aimed to evaluate the potential of a novel ecological niche of 374 fungus-growing termite associated Natural Products (NPs). The molecular docking and computational pharmacokinetics screened four compounds, i.e., Termstrin B, Fridamycin A, Maduralactomycin A, and Natalenamide C, as potential compounds that have higher binding affinities and favourable protein-ligand interactions. The compound Maduralactomycin A induced more stability based on its lowest average RMSD value (2.31 Å) and low standard deviation (0.35) supported by the consistent flexibility and β-factor during the protein’s time-dependent motion. While hydrogen bond analysis indicated that Termstrin B has formed the strongest intra-protein interaction, solvent accessibility was in good agreement with Maduralactomycin A compactness. Maduralactomycin A has the strongest binding energy among all the compounds (−348.48 kcal/mol) followed by Termstrin B (−321.19 kcal/mol). Since these findings suggest Maduralactomycin A and Termstrin B as promising candidates for inhibition of MurF protein, the favourable binding energies of Maduralactomycin A make it a more important compound to warrant further investigation. However, experimental validation using animal models and clinical trials is recommended before reaching any final conclusions.
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影响因子：
4.9
作者：
Baum, Ellen Z.;Crespo-Carbone, Steven M.;Bush, Karen
通讯作者：
Bush, Karen
DOI：
10.3390/v15020570
发表时间：
2023-02-19
期刊：
Viruses
影响因子：
--
作者：
Ali Y;Imtiaz H;Tahir MM;Gul F;Saddozai UAK;Ur Rehman A;Ren ZG;Khattak S;Ji XY
通讯作者：
Ji XY
影响因子：
4.6
作者：
Lee MK;Lee KH;Yoo SH;Park CY
通讯作者：
Park CY
影响因子：
--
作者：
Comess, Kenneth M.;Schurdak, Mark E.;Beutel, Bruce A.
通讯作者：
Beutel, Bruce A.
影响因子：
4.6
作者：
Daina A;Michielin O;Zoete V
通讯作者：
Zoete V