Journal of the Korean Magnetic Resonance Society (한국자기공명학회논문지)

Korean Magnetic Resonance Society (한국자기공명학회)
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Effects of Substitutions of Gln16 and Asp18 with Phe or Tyr in HP(2-20) on its Structure and Antimicrobial Activity

  • Kim, Jin-Kyoung (Department of Bioscience and Biotechnology, Bio/informatics center, Konkuk University) ;
  • Lee, Ju-Un (Department of Bioscience and Biotechnology, Bio/informatics center, Konkuk University) ;
  • Kim, Woong-Hee (Department of Bioscience and Biotechnology, Bio/informatics center, Konkuk University) ;
  • Park, Yoon-Kyung (Department of Biotechnology and BK21 Research Team for Protein Activity control, Chosun University) ;
  • Hahm, Kyung-Soo (Department of Bio-Materials, Graduate School and Research Center for Proteineous Materials, Chosun University) ;
  • Kim, Yang-Mee (Department of Bioscience and Biotechnology, Bio/informatics center, Konkuk University)
  • Published : 2009.06.20
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Abstract

HP (2-20), a 19-residue peptide derived from the N-terminus of Helicobacter pylori Ribosomal Protein L1, has antimicrobial activity but is not cytotoxic to human erythrocytes. Previously, we have synthesized several analogue peptides to investigate the effects of substitutions on the structure and antimicrobial activity. Substitution of $Gln^{16}$ and $Asp^{18}$ with Trp (Anal 3) caused a dramatic increase in bacterial and fungal lytic activities. In this study, analogue peptides were synthesized to investigate the effects of substitution of Gin and Asp with Phe (Anal 6) or Tyr (Anal 7) in HP (2-20) on its structure and antimicrobial activity. Substitution of Gin and Asp with hydrophobic aromatic residues at position 16 and 18 of HP (2-20) caused increase in antibiotic activity without hemolytic effect. Substitution of Gin and Asp with Trp and Try increased antibiotic activity of HP (220) twice more compared to substitution with Phe. The tertiary structures of Anal 6 and Anal 7 in SDS micelles has been investigated using NMR spectroscopy. The structures revealed that substitutions of the aromatic residues at C-terminus resulted in longer and well defined alpha-helix and improved their antibacterial activities

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References

  1. H. G. Boman J. Intern. Med. 254, 197 (2003). https://doi.org/10.1046/j.1365-2796.2003.01228.x
  2. M. Zasloff Nature 415, 389 (2002). https://doi.org/10.1038/415389a
  3. D. Barra and M. Simmaco Trends Biotechnol. 13, 205 (1995). https://doi.org/10.1016/S0167-7799(00)88947-7
  4. D. G. Lee, P. I. Kim, Y. Park, S. H. Jang, S. C. Park, E. R Woo, K. S. Hahm J. of Peptide Science 8, 453 (2002). https://doi.org/10.1002/psc.405
  5. K. H. Lee, D. G.Lee, Y. Park, D. I. Kang, S. Y. Shin, K. S. Hahm, Y. Kim Biochem. J. 394, 1056 (2006).
  6. A. Derome and M. Willamson, J. Magn. Reson. 88, 177 (1990).
  7. A. Bax and D. G. Davis, J. Magn. Reson. 65, 355 (1985).
  8. S. Macura and R.R. Ernst, Mol. Phys. 41, 95 (1980). https://doi.org/10.1080/00268978000102601
  9. A. Bax and D. G. Davis, J. Magn. Reson. 63, 207 (1985).
  10. G. Bodenhausen and D. J. Ruben, J. Chem. Phys. Lett. 69, 185 (1980). https://doi.org/10.1016/0009-2614(80)80041-8
  11. A. T. Brunger, X-PLOR Manual, Version 3.1, Yale University, New Haven, CT (1993).
  12. G. M. Clore and A. M. Gronenborn, CRC. Rev. in Biochem. BioI. 24,479 (1989). https://doi.org/10.3109/10409238909086962
  13. G. M. Clore and A. M. Gronenborn, Protein Science 3, 372 (1994). https://doi.org/10.1002/pro.5560030302
  14. K. Wuthrich, M. Billeter, and W. Braun, J. Mol. BioI. 169, 949 (1983). https://doi.org/10.1016/S0022-2836(83)80144-2
  15. G. M. Clore, A. M. Gronenborn, M. Nilges, and C. A. Ryan, Biochemistry 26, 8012-8023(1987). https://doi.org/10.1021/bi00398a069
  16. M. Nilges, G. M. Clore, and A.M. Gronenborn, FEBS Lett. 229, 317 (1988). https://doi.org/10.1016/0014-5793(88)81148-7
  17. A. Chattopadhyay, S. S. Rawat, D. V. Greathouse, D. A. Kelkar, R E. Koeppe, Biophys. J. 95(1), 166 (2008). https://doi.org/10.1529/biophysj.107.124206
  18. R. Domanov, Y. Pietiainen, V. P. Kontinen, P. K. Kinnunen Biochim Biophys Acta1778(4) 983 (2008). https://doi.org/10.1016/j.bbamem.2007.11.016