Durai Prasannavenkatesh, Lee Yeongjoon, Kim Jieun, Jeon Dasom, Kim Yangmee
Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea.
J Microbiol Biotechnol. 2018 May 28;28(5):671-678. doi: 10.4014/jmb.1801.01025.
Papiliocin, isolated from the swallowtail butterfly (), is an antimicrobial peptide with high selectivity against gram-negative bacteria. We previously showed that the N-terminal helix of papiliocin (PapN) plays a key role in the antibacterial and anti-inflammatory activity of papiliocin. In this study, we measured the selectivity of PapN against multidrug-resistant gram-negative bacteria, as well as its anti-inflammatory activity. Interactions between Trp2 of PapN and lipopolysaccharide (LPS), which is a major component of the outer membrane of gram-negative bacteria, were studied using the Trp fluorescence blue shift and quenching in LPS micelles. Furthermore, using circular dichroism, we investigated the interactions between PapN and LPS, showing that LPS plays critical roles in peptide folding. Our results demonstrated that Trp2 in PapN was buried deep in the negatively charged LPS, and Trp2 induced the α-helical structure of PapN. Importantly, docking studies determined that predominant electrostatic interactions of positively charged arginine residues in PapN with phosphate head groups of LPS were key factors for binding. Similarly, hydrophobic interactions by aromatic residues of PapN with fatty acid chains in LPS were also significant for binding. These results may facilitate the development of peptide antibiotics with anti-inflammatory activity.
从燕尾蝶中分离出的papiliocin是一种对革兰氏阴性菌具有高选择性的抗菌肽。我们之前表明，papiliocin的N端螺旋（PapN）在papiliocin的抗菌和抗炎活性中起关键作用。在本研究中，我们测定了PapN对多重耐药革兰氏阴性菌的选择性及其抗炎活性。利用色氨酸荧光蓝移和在脂多糖（LPS）胶束中的猝灭现象，研究了PapN的色氨酸2（Trp2）与革兰氏阴性菌外膜主要成分脂多糖之间的相互作用。此外，利用圆二色性，我们研究了PapN与LPS之间的相互作用，结果表明LPS在肽折叠中起关键作用。我们的结果表明，PapN中的Trp2深埋于带负电荷的LPS中，且Trp2诱导了PapN的α螺旋结构。重要的是，对接研究确定，PapN中带正电荷的精氨酸残基与LPS磷酸头部基团之间的主要静电相互作用是结合的关键因素。同样，PapN的芳香族残基与LPS中的脂肪酸链之间的疏水相互作用对结合也很重要。这些结果可能有助于开发具有抗炎活性的肽类抗生素。
