title: Influence of Cysteine and Tryptophan Substitution on DNA-Binding Activity on Maize α-Hairpinin Antimicrobial Peptide.
abstract: For almost four decades, antimicrobial peptides have been studied, and new classes are being discovered. However, for therapeutic use of these molecules, issues related to the mechanism of action must be answered. In this work, the antimicrobial activity of the hairpinin MBP-1 was studied by the synthesis of two variants, one replacing cysteines and one tryptophan with alanine. Antibacterial activity was abolished in both variants. No membrane disturbance, even in concentrations higher than those required to inhibit the bacteria, was observed in SEM microscopy. The gel retardation assay showed that MBP-1 possesses a higher DNA-binding ability than variants. Finally, molecular modelling showed that the lack of cysteines resulted in structure destabilization and lack of tryptophan resulted in a less flexible peptide, with less solvent assessable surface area, both characteristics that could contribute to absence of activity. In summary, the data here reported add more information about the multiple mechanisms of action of α-hairpinins.
authors.affiliation: Programa de Pós Graduação em Patologia Molecular, Universidade de Brasília, Brasília, DF 70910-900, Brazil. amarods@gmail.com.|Centro de Análises Proteômicas e Bioquímicas, Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília, DF 70790-160, Brazil. amarods@gmail.com.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Sousa
authors.affiliation: Centro de Análises Proteômicas e Bioquímicas, Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília, DF 70790-160, Brazil. Williamfp7@gmail.com.
authors.forename: William F
authors.initials: WF
authors.lastname: Porto
authors.affiliation: Centro de Análises Proteômicas e Bioquímicas, Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília, DF 70790-160, Brazil. marizaban@gmail.com.
authors.forename: Maria Z
authors.initials: MZ
authors.lastname: Silva
authors.affiliation: Centro de Análises Proteômicas e Bioquímicas, Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília, DF 70790-160, Brazil. tatyrodrigues8@gmail.com.
authors.forename: Tatiane R
authors.initials: TR
authors.lastname: da Silva
authors.affiliation: Programa de Pós Graduação em Patologia Molecular, Universidade de Brasília, Brasília, DF 70910-900, Brazil. ocfranco@pos.ucb.br.|Centro de Análises Proteômicas e Bioquímicas, Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília, DF 70790-160, Brazil. ocfranco@pos.ucb.br.|S-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Catolica Dom Bosco, Campo Grande, MS 79117-900, Brazil. ocfranco@pos.ucb.br.
authors.forename: Octávio L
authors.initials: OL
authors.lastname: Franco
mesh_terms: D019943:Amino Acid Substitution; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D003545:Cysteine / Q000737:chemistry*; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000737:chemistry*; D003313:Zea mays / Q000737:chemistry*
chemical_list: D023181:Antimicrobial Cationic Peptides; D014364:Tryptophan; D004247:DNA; D003545:Cysteine
keywords: DNA-binding; antimicrobial peptides; α-hairpinin