Structure-Activity Relationship of the N-terminal Helix Analog of Papiliocin, PapN
1
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Papiliocin, from the swallowtail butterfly, Papilio xuthus, shows high bacterial cell selectivity against Gram-negative bacteria. Recently, we designed a 22mer analog with N-terminal helix from Lys3 to Ala22, PapN. It shows outstanding antimicrobial activity against Gram-negative bacteria with low toxicity against mammalian cells. In this study, we determined the 3-D structure of PapN in 300 mM DPC micelle using NMR spectroscopy and investigated the interactions between PapN and DPC micelles. The results showed that PapN has an amphipathic α-helical structure from Lys3 to Lys21. STD-NMR and DOSY experiment showed that this helix is important in binding to the bacterial cell membrane. Furthermore, we tested antibacterial activities of PapN in the presence of salt for therapeutic application. PapN was calcium- and magnesium-resistant in a physiological condition, especially against Gram-negative bacteria, implying that it can be a potent candidate as peptide antibiotics.
Abstract
Papiliocin, from the swallowtail butterfly, Papilio xuthus, shows high bacterial cell selectivity against Gram-negative bacteria. Recently, we designed a 22mer analog with N-terminal helix from Lys3 to Ala22, PapN. It shows outstanding antimicrobial activity against Gram-negative bacteria with low toxicity against mammalian cells. In this study, we determined the 3-D structure of PapN in 300 mM DPC micelle using NMR spectroscopy and investigated the interactions between PapN and DPC micelles. The results showed that PapN has an amphipathic α-helical structure from Lys3 to Lys21. STD-NMR and DOSY experiment showed that this helix is important in binding to the bacterial cell membrane. Furthermore, we tested antibacterial activities of PapN in the presence of salt for therapeutic application. PapN was calcium- and magnesium-resistant in a physiological condition, especially against Gram-negative bacteria, implying that it can be a potent candidate as peptide antibiotics.
참고문헌 (23)
- E. Guaní-Guerra, , Clin Immunol, 135, pp.1~ (2010)
- P. Bulet, , Immunol Rev, 198, pp.169~ (2004)
- R. E. Hancock, , Trends Biotechnol, 16, pp.82~ (1998)
- S. E. Blondelle, , Biochem Biophys Acta, 1462, pp.89~ (1999)
- R. E. Hancock, , Nat Biotechnol, 24, pp.1551~ (2006)
- K. A. Brogden, , Nat Rev Microbial, 3, pp.238~ (2005)
- E. Lee, , Biochem Biophys Acta, 1828, pp.271~ (2013)
- Seong Ryul Kim, "Characterization and cDNA Cloning of a Cecropin-Like Antimicrobial Peptide, Papiliocin, from the Swallowtail Butterfly, Papilio xuthus", Molecules and Cells, 29(4), pp.419~423 (2010), 한국분자세포생물학회
- J. -K. Kim, , J. Biol. Chem, 286, pp.41296~ (2011)
- E. Lee, , Scientific reports, 5, pp.12048~ (2015)
- A. Derome, , J. Magn. Reson, 88, pp.177~ (1990)
- A. Bax, , J. Magn. Reson, 65, pp.355~ (1985)
- A. Bax, , J. Magn. Reson, 64, pp.207~ (1985)
- D. Marion, , Biochem Biophys Res Commun, 113, pp.967~ (1983)
- F. Delaglio, , J. Biomol. NMR, 6, pp.277~ (1995)
- T. D. Goddard, "Sparky 3", University of California, ~
- P. Güntert, , Methods Mol Bio, 278, pp.353~ (2004)
- 김진경, "Structure-Activity Relationships of 9-mer Antimicrobial Peptide analogue of Protaetiamycine, 9Pbw2", Journal of the Korean Magnetic Resonance Society, 15(1), pp.1~13 (2011), 한국자기공명학회
- K. F. Morris, , J. Am. Chem, 114, pp.3139~ (1992)
- A. M. Cole, , Agents. Chemother, 44, pp.2039~ (2000)
- 김원제, "Enhanced Chemical Shift Analysis for Secondary Structure prediction of protein", Journal of the Korean Magnetic Resonance Society, 18(1), pp.36~40 (2014), 한국자기공명학회[DOI]
- 이고은, "1H, 15N, and 13C backbone assignments and secondary structure of the cytoplasmic domainA of mannitol trasporter IIMannitol from Thermoanaerobacter Tencongensis phosphotransferase system", Journal of the Korean Magnetic Resonance Society, 19(1), pp.42~48 (2015), 한국자기공명학회[DOI]
- D. S. Wishart, , Biochemistry, 31, pp.1647~1651 (1992)