title: Native and recombinant Pg-AMP1 show different antibacterial activity spectrum but similar folding behavior.
abstract: Glycine-rich proteins (GRPs) derived from plants compose a family of proteins and peptides that share a glycine repeat domain and they can perform diverse functions. Two structural conformations have been proposed for GRPs: glycine loops arranged as a Velcro and an anti-parallel β-sheet with several β-strands. The antimicrobial peptide Pg-AMP1 is the only plant GRP with antibacterial activity reported so far and its structure remains unclear. Recently, its recombinant expression was reported, where the recombinant peptide had an additional methionine residue at the N-terminal and a histidine tag at the C-terminal (His6-tag). These changes seem to change the peptide's activity, generating a broader spectrum of antibacterial activity. In this report, through ab initio molecular modelling and molecular dynamics, it was observed that both native and recombinant peptide structures were composed of an N-terminal α-helix and a dynamic loop that represents two-thirds of the protein. In contrast to previous reports, it was observed that there is a tendency to adopt a globular fold instead of an extended one, which could be in both, glycine loops or anti-parallel β-sheet conformation. The recombinant peptide showed a slightly higher solvated potential energy compared to the native form, which could be related to the His6-tag exposition. In fact, the His6-tag could be mainly responsible for the broader spectrum of activity, but it does not seem to cause great structural changes. However, novel studies are needed for a better characterization of its pharmacological properties so that in the future novel drugs may be produced based on this peptide.
authors.affiliation: Centro de Análises Proteômicas e Bioquímicas, Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília, DF, Brazil.
authors.forename: William F
authors.initials: WF
authors.lastname: Porto
authors.affiliation: Centro de Análises Proteômicas e Bioquímicas, Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília, DF, Brazil; Curso de Física, Universidade Católica de Brasília, Brasília, DF, Brazil.
authors.forename: Diego O
authors.initials: DO
authors.lastname: Nolasco
authors.affiliation: Centro de Análises Proteômicas e Bioquímicas, Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília, DF, Brazil. Electronic address: ocfranco@gmail.com.
authors.forename: Octavio L
authors.initials: OL
authors.lastname: Franco
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D056004:Molecular Dynamics Simulation; D010940:Plant Proteins / Q000737:chemistry* / Q000494:pharmacology; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology
chemical_list: C000588960:AMP1 protein, Psidium guajava; D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D010940:Plant Proteins; D011994:Recombinant Proteins
keywords: Ab initio molecular modelling; Antimicrobial peptides; Molecular dynamics; Plant glycine-rich proteins; Solvated potential energy