Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand.
Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Int J Mol Sci. 2021 Nov 17;22(22):12401. doi: 10.3390/ijms222212401.
Human α-defensin 5 (HD5) is a host-defense peptide exhibiting broad-spectrum antimicrobial activity. The lipopolysaccharide (LPS) layer on the Gram-negative bacterial membrane acts as a barrier to HD5 insertion. Therefore, the pore formation and binding mechanism remain unclear. Here, the binding mechanisms at five positions along the bacterial membrane axis were investigated using Molecular Dynamics. (MD) simulations. We found that HD5 initially placed at positions 1 to 3 moved up to the surface, while HD5 positioned at 4 and 5 remained within the membrane interacting with the middle and inner leaflet of the membrane, respectively. The arginines were key components for tighter binding with 3-deoxy-d-manno-octulosonic acid (KDO), phosphates of the outer and inner leaflets. KDO appeared to retard the HD5 penetration.
人α-防御素 5 (HD5) 是一种具有广谱抗菌活性的宿主防御肽。革兰氏阴性细菌膜上的脂多糖 (LPS) 层充当 HD5 插入的屏障。因此，其孔形成和结合机制尚不清楚。在这里，使用分子动力学 (MD) 模拟研究了沿细菌膜轴的五个位置的结合机制。我们发现，最初位于位置 1 到 3 的 HD5 移动到表面，而位于位置 4 和 5 的 HD5 保持在膜内，分别与膜的中间和内叶相互作用。精氨酸是与 3-脱氧-d-甘露庚酮糖酸 (KDO)、外叶和内叶的磷酸基团紧密结合的关键组成部分。KDO 似乎阻碍了 HD5 的渗透。
