A novel cation− π interaction between the bound Cu+ metal ion and Trp44 in the periplasmic
Cu+/Ag+ metallochaperone Escherichia coli CusF protects Cu+ from the oxidative influence
of the periplasm. In a popular model of metal ion transfer, a conformational change in the
metal binding loop disrupts the cation− π interaction and moves Trp44 aside to provide
access to the occluded metal ion binding site in an “open” conformation. In this study, our
molecular dynamics simulations support this putative mechanism of metal ion transfer. We …