title: Is there a difference in metal ion-based inhibition between members of thionin family: Molecular dynamics simulation study.
abstract: Thionins have a considerable potential as antimicrobial compounds although their application may be restricted by metal ion-based inhibition of membrane permeabilizing activity. We previously reported the properties associated with the proposed mechanism of metal ion-based inhibition of beta-purothionin. In this study, we investigated the effects of metal ions on alpha-hordothionin which differs from beta-purothionin by eight out of 45 residues. Three of the differing residues are thought to be involved in the mechanism of metal ion-based inhibition in beta-purothionin. The structure and dynamics of alpha-hordothionin were explored using unconstrained molecular dynamics (MD) simulations in explicit water as a function of metal ions. Although the global fold is almost identical to that of beta-purothionin, alpha-hordothionin displays reduced fluctuating motions. Moreover, alpha-hordothionin is more resistant to the presence of metal ions than beta-purothionin. Mg(+2) ions do not affect alpha-hordothionin, whereas K(+) ions induce perturbations in the alpha2 helix, modify dynamics and electrostatic properties. Nevertheless, these changes are considerably smaller than those in beta-purothionin. The proposed mechanism of metal ion-based inhibition involves the hydrogen bonding network of Arg5-Arg30-Gly27, which regulates dynamic unfolding of the alpha2 C-end which is similar to beta-purothionin response. The key residues responsible for the increased resistance for alpha-hordothionin are Gly27 and Gly42 which replace Asn27 and Asp42 involved into the mechanism of metal ion-based inhibition in beta-purothionin. Comparison of MD simulations of alpha-hordothionin with beta-purothionin reveals dynamic properties which we believe are intrinsic properties of thionins with four disulphide bonds.
authors: LSU AgCenter Biotechnology Laboratory, Louisiana State University, 115 Wilson Bldg., LSU, Baton Rouge, LA 70803, USA. soard@agctr.lsu.edu
authors: Svetlana
authors: S
authors: Oard
authors: Bijaya
authors: B
authors: Karki
authors: Frederick
authors: F
authors: Enright
mesh_terms: D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000037:antagonists & inhibitors* / Q000737:chemistry; D023181:Antimicrobial Cationic Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry; D002413:Cations, Divalent / Q000737:chemistry; D002414:Cations, Monovalent / Q000737:chemistry; D003198:Computer Simulation; D006860:Hydrogen Bonding; D008274:Magnesium / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011188:Potassium / Q000737:chemistry*; D017433:Protein Structure, Secondary; D055672:Static Electricity
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D002413:Cations, Divalent; D002414:Cations, Monovalent; D010940:Plant Proteins; C036092:hordothionin protein, Hordeum vulgare; C016085:purothionin; D008274:Magnesium; D011188:Potassium