Koo, Young Sook Kim, Jung Min Park, In Yup Yu, Byung Jo Jang, Su A. Kim, Key-Sun Park, Chan Bae Cho, Ju Hyun Kim, Sun Chang 2024-01-20T23:02:50Z 2024-01-20T23:02:50Z 2021-09-03 2008-07 0196-9781 https://pubs.kist.re.kr/handle/201004/133349 The structure-activity relations and mechanism of action of parasin I, a 19-amino acid histone H2A-derived antimicrobial peptide, were investigated. Parasin I formed an amphipathic a-helical structure (residues 9-17) flanked by two random coil regions (residues 1-8 and 18-19) in helix-promoting environments. Deletion of the lysine residue at the N-terminal [Pa(2-19)] resulted in loss of antimicrobial activity, but did not affect the a-helical content of the peptide. The antimicrobial activity was recovered when the lysine residue was substituted with another basic residue, arginine ([R-1]Pa), but not with polar, neutral, or acidic residues. Progressive deletions from the C-terminal [Pa(1-17), Pa(1-15)] slightly increased the antimicrobial activity (1-1 mu g/ml) without affecting the a-helical content of the peptide. However, further deletion [Pa(1-14)] resulted in nearly complete loss of antimicrobial activity and a-helical structure. Confocal microscopic analysis and membrane permeabilization assays showed that parasin I and its analogs with comparable antimicrobial activities localized to the cell membrane and subsequently permeabilized the outer and cytoplasmic membranes. Pa(1-14) also localized to the cell membrane, but lost membrane-permeabilizing activity, whereas Pa(2-19) showed poor membrane-binding and permeabilizing activities. The results indicate that the basic residue at the N-terminal is essential for the membrane-binding activity of parasin I, and among the membrane-binding parasin I analogs, the a-helical structure is necessary for the membrane-permeabilizing activity. (C) 2008 Elsevier Inc. All rights reserved. English ELSEVIER SCIENCE INC Structure-activity relations of parasin I, a histone H2A-derived antimicrobial peptide Article 10.1016/j.peptides.2008.02.019 1 PEPTIDES, v.29, no.7, pp.1102 - 1108 PEPTIDES 29 7 1102 1108 N scie scopus 000257489100004 2-s2.0-44649183244 Biochemistry & Molecular Biology Endocrinology & Metabolism Pharmacology & Pharmacy Biochemistry & Molecular Biology Endocrinology & Metabolism Pharmacology & Pharmacy Article AMPHIPATHIC HELIX SKIN MUCOSA CONFORMATION RESISTANCE MECHANISMS MAGAININS BACTERIA DEFENSE CATFISH MODEL parasin I histone H2A antimicrobial peptide membrane permeabilization