Is there a difference in metal ion-based inhibition between members of thionin family: Molecular dynamics simulation study

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, a-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 alpha 2 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-Arg3O-Gly27, which regulates dynamic unfolding of the alpha 2 C-end which is similar to beta-purothionin response. The key residues responsible for the increased resistance for a-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 a-hordothionin with beta-purothionin reveals dynamic properties which we believe are intrinsic properties of thionins with four disulphide bonds. (c) 2007 Elsevier B.V All rights reserved.