Title
Conformation-dependent antibiotic activity of tritrpticin, a cathelicidin-derived antimicrobial peptide
Author
Sung-Tae Yang, Song Yub Shin, Yong-Chul Kim, Yangmee Kim, Kyung-Soo Hahm, Jae Il Kim
Year
2002
Journal
Biochemical and Biophysical Research Communications
Abstract
Tritrpticin, a Trp-rich cationic antimicrobial peptide with a unique amino acid sequence (VRRFPWWWPFLRR), is found in porcine cathelicidin cDNA. Tritrpticin has a broad spectrum of antibacterial and antifungal activities and hemolytic activity comparable to that of indolicidin. To investigate the mechanism of the bacterial killing action of tritrpticin and to identify structural features important for bacterial cell selectivity, we designed several tritrpticin analogs with amino acid substitutions of the Pro and Trp residues. Circular dichroism studies revealed that the substitution of Pro → Ala (TPA) or Trp → Phe (TWF) leads to significant conformational changes in SDS micelles, converting the β-turn to α-helix or to poly-l-proline II helix, respectively. Compared to tritrpticin, TPA retained most of its antimicrobial activity, but showed enhanced hemolytic and membrane-disrupting activities. In contrast, TWF showed a 2–4-fold increase in antimicrobial activity against Gram-negative bacteria, but a marked decrease in both hemolytic and membrane-disrupting activities. Taken together, our findings suggest that compared with the β-turn and α-helical structures, the poly-l-proline II helix is crucial for effective bacterial cell selectivity in tritrpticin and its analogs.
Instrument
J-715
Keywords
Circular dichroism, Secondary structure, Vesicle interactions, Biochemistry