Computational study of the role of Tryptophan in the binding site ofCu(I) and Ag(I) in the protein CusF

DALOSTO, S

Salta

Congreso; 3rd Latin American Protein Society Meeting in 2010; 2010

This communication reports the role of the conserved tryptophan in the periplasmic protein CusF in defining the binding site stability of Cu(I) and Ag(I) addressed using quantum mechanics in combination with molecular mechanics. In CusF proteins, Cu(I)/Ag(I) binds to one histidine (His), two methionine (Met) and a tryptophan (Trp) residues in a trigonal distorted arrange, Cu(I)-Met2His with, TRP in the apical position. Here it is shown that the Trp pulls the Cu(I)/Ag(I) out of the plane defined by Met2His due to a strong cation-p interaction. In order to better understand the Trp – Cu(I)/Ag(I)-Met2His interaction, the Trp was replaced by Gly. It is found that both Cu(I) and Ag(I) move to the plane Met2His confirming the cation-p interaction and allowing to estimate the energetic changes. A possible scenario for the copper translocation between CusF and other metallochaperon proteins is discussed.