在硅基上对佐苏拉宾与嗜肺军团菌、肺炎军团菌和博兹曼军团菌中LptB2FG的结合进行分析：其差异疗效的潜在机制
In silico analysis of zosurabalpin-LptB2FG binding in spp., , and : mechanisms underlying its differential efficacy.
作者信息
Magri Meryam, Eljaoudi Rachid, Belyamani Lahcen, Ibrahimi Azeddine, Bouricha El Mehdi
机构信息
Medical Biotechnology Laboratory (MedBiotech), Faculty of Medicine and Pharmacy of Rabat, Mohammed Vth University in Rabat, Rabat, Morocco.
Mohammed VI University of Sciences and Health (UM6SS), Casablanca, Morocco.
出版信息
In Silico Pharmacol. 2025 Apr 16;13(2):62. doi: 10.1007/s40203-025-00343-3. eCollection 2025.
UNLABELLED
Zosurabalpin, a novel tethered macrocyclic peptide antibiotic, exhibits potent activity against spp., particularly carbapenem-resistant (CRAB). Zosurabalpin inhibits lipopolysaccharide (LPS) transport by targeting the LptB2FG protein complex, resulting in toxic LPS accumulation and bacterialdeath. This study investigates zosurabalpin's molecular specificity against spp., its ineffectiveness against , and its potential efficacy against . Comparative analysis of LptB2FG sequences and structures, revealed significant differences in LptB2FG protein conformations, pocket geometry and electrostatic surface surrounding the binding pocket among the three species, which may influence zosurabalpin binding. Docking results for zosurabalpin showed lower binding affinities for and compared to . Additionally, other zosurabalpin derivatives were tested showing improved binding affinities for but not for . These findings underscore the need for tailored zosurabalpin derivatives to enhance efficacy against a broader spectrum of Gram-negative bacteria.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40203-025-00343-3.
未标记
佐苏拉巴尔平是一种新型的连接大环肽抗生素，对[具体菌种]具有强大活性，尤其是对耐碳青霉烯类[具体菌种]（CRAB）。佐苏拉巴尔平通过靶向LptB2FG蛋白复合物抑制脂多糖（LPS）转运，导致有毒LPS积累和细菌死亡。本研究调查了佐苏拉巴尔平对[具体菌种]的分子特异性、对[其他菌种]无效的原因以及对[另一菌种]的潜在疗效。对LptB2FG序列和结构的比较分析表明，这三种菌种的LptB2FG蛋白构象、口袋几何形状以及结合口袋周围的静电表面存在显著差异，这可能会影响佐苏拉巴尔平的结合。佐苏拉巴尔平的对接结果显示，与[某菌种]相比，其对[另外两种菌种]的结合亲和力较低。此外，还测试了其他佐苏拉巴尔平衍生物，结果表明它们对[某菌种]的结合亲和力有所提高，但对[另一菌种]没有提高。这些发现强调了需要定制佐苏拉巴尔平衍生物以增强对更广泛革兰氏阴性菌的疗效。
补充信息
在线版本包含可在10.1007/s40203-025-00343-3获取的补充材料。
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