Influence of $${\text{NH - }}{{\text{S}}^\gamma }$$ bonding interactions on the structure and dynamics of metallothioneins

Abstract

Mammalian metallothioneins ($${\text{M}}_7^{\text{IIMTs}}$$) show a clustered arrangement of the metal ions and a nonregular protein structure. The solution structures of Cd3-thiolate cluster containing β-domain of mouse β-MT-1 and rat β-MT-2 show high structural similarities, but widely differing structure dynamics. Molecular dynamics simulations revealed a substantially increased number of $${\text{NH - }}{{\text{S}}^\gamma }$$ hydrogen bonds in β-MT-2, features likely responsible for the increased stability of the Cd3-thiolate cluster and the enfolding protein domain. Alterations in the $${\text{NH - }}{{\text{S}}^\gamma }$$ hydrogen-bonding network may provide a rationale for the differences in dynamic properties encountered in the β-domains of MT-1, -2, and -3 isoforms, believed to be essential for their different biological functio