Influence of NH-Sγ bonding interactions on the structure and dynamics of metallothioneins

Mammalian metallothioneins ((M7MTs)-M-II) show a clustered arrangement of the metal ions and a nonregular protein structure. The solution structures of Cd-3-thiolate cluster containing beta-domain of mouse beta-MT-1 and rat beta-MT-2 show high structural similarities, but widely differing structure dynamics. Molecular dynamics simulations revealed a substantially increased number of NH-S-gamma hydrogen bonds in beta-MT-2, features likely responsible for the increased stability of the Cd-3-thiolate cluster and the enfolding protein domain. Alterations in the NH-S-gamma hydrogen-bonding network may provide a rationale for the differences in dynamic properties encountered in the beta-domains of MT-1, -2, and -3 isoforms, believed to be essential for their different biological function.