PDF(Pubmed)
Abstract：
Infections caused by Staphylococcus aureus are currently a worldwide threat affecting millions of individuals. The pathogenicity of S. aureus is associated with numerous virulence factors, including cell surface proteins, polysaccharides, and secreted toxins. The pore-forming α-hemolysin, known as α-toxin, is produced by nearly all virulent strains of S. aureus and is implicated in several diseases including skin and soft tissue infections, atopic dermatitis, and pneumonia. There are currently no vaccines available for the prevention of S. aureus infections and the efficacy of available antibiotics has been fading. In this study we examined the mode of antihemolytic activity of theaflavin-3,3\'-digallate against α-hemolysin of methicillin-resistant S. aureus by molecular docking using AutoDock Vina as the molecular docking tool. The theaflavin-3,3\'-digallate docked the molecular sequence of the Hla (PDB ID:7ahl). The scores of the top 10 binding modes obtained were between -9.0 and -8.5 kcal mol-1, and the best binding mode was -9.0 kcal mol-1. Direct binding sites of theaflavin-3,3\'-digallate to the \"stem\" domain of Hla were revealed which primarily targeted of the residues Met113, Thr117, Asn139. The disclosure of this potential binding mode warrants further clinical evaluation of theaflavin-3,3\'-digallate as an anti-hemolytic compound in order to practically validate our results.
摘要：
由金黄色葡萄球菌引起的感染目前是影响数百万人的全球威胁。金黄色葡萄球菌的致病性与多种毒力因子有关,包括细胞表面蛋白，多糖，分泌毒素.成孔α-溶血素，被称为α毒素，由几乎所有的金黄色葡萄球菌毒力菌株产生，并与包括皮肤和软组织感染在内的多种疾病有关，特应性皮炎,和肺炎。目前没有可用于预防金黄色葡萄球菌感染的疫苗,并且可获得的抗生素的效力正在消退。在这项研究中，我们使用AutoDockVina作为分子对接工具，通过分子对接研究了茶黄素-3,3'-digalate抗耐甲氧西林金黄色葡萄球菌的α-溶血素的抗溶血活性模式。茶黄素-3,3'-二等位基因对接Hla的分子序列(PDBID:7ahl)。获得的前10种结合模式的得分在-9.0至-8.5kcalmol-1之间，最佳结合模式为-9.0kcalmol-1。揭示了茶黄素-3,3'-digalate与Hla的“茎”结构域的直接结合位点，主要靶向残基Met113，Thr117，Asn139。这种潜在结合模式的公开保证了对茶黄素-3,3'-二烷基酯作为抗溶血化合物的进一步临床评估，以实际验证我们的结果。
