Disperse Distribution of Cationic Amino Acids on Hydrophilic Surface of Helical Wheel Enhances Antimicrobial Peptide Activity
SCIE
SCOPUS
- Title
- Disperse Distribution of Cationic Amino Acids on Hydrophilic Surface of Helical Wheel Enhances Antimicrobial Peptide Activity
- Authors
- Kim, YS; Cha, HJ
- Date Issued
- 2010-10-01
- Publisher
- JOHN WILEY & SONS INC
- Abstract
- The antimicrobial action of amphipathic antimicrobial peptides (AMPs) generally depends on perturbation of the bacterial membrane via electrostatic interactions promoting initial binding to the surface and hydrophobic interactions for pore formation into the membrane. Several studies have focused on the structure-activity relationship (SAR) of AMPs by modulation of structural parameters. However, modulation of one parameter commonly induces simultaneous changes in other parameters, making it difficult to investigate the specific influence of a single variable. In the present work, we investigated the distribution effect of cationic amino acids on the hydrophilic surface of the helical wheel using model AMPs composed of only lysine (K) and leucine (L) as representative cationic and hydrophobic residues, respectively, under conditions in which other parameters are fixed. Based on SAR analyses of alpha-helical KL model AMPs displaying different cationic distributions, we propose that the dispersity of cationic amino acids on the hydrophilic surface is a factor that contributes to the antimicrobial activity of AMP. Moreover, antimicrobial activity is enhanced by rearrangement of cationic amino acids to promote dispersed distribution. We confirmed the cationic distribution effect using natural AMP-derived alpha-helical CRAMP18 and its analogs. Our data show that accumulation of lysine shifts in the CRAMP18 analog leads to higher dispersion, and subsequently to improved antimicrobial activity. Therefore, we propose that the cationic distribution effect can be applied for the rational redesign of amino acid sequences to improve the antimicrobial activities of natural alpha-helical AMPs, in combination with regulation of other known structural parameters. Biotechnol. Bioeng. 2010;107: 216-223. (c) 2010 Wiley Periodicals, Inc.
- Keywords
- antimicrobial peptide; cationic amino acid distribution; structure-activity relationship; RESONANCE ENERGY-TRANSFER; HYDROPHOBIC MOMENT; HEMOLYTIC-ACTIVITY; MODEL MEMBRANES; ANTIBACTERIAL; PROTEINS; ANGLE; MECHANISMS; ANALOGS; DESIGN
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/25349
- DOI
- 10.1002/BIT.22810
- ISSN
- 0006-3592
- Article Type
- Article
- Citation
- BIOTECHNOLOGY AND BIOENGINEERING, vol. 107, no. 2, page. 216 - 223, 2010-10-01
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