Computational study of the tryptophan role in the binding site of Cu(I) and Ag(I) in the protein CusF

DALOSTO, S

Santa Fe

Workshop; 4to. Workshop de Quimica Bioinorganica; 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. The potential energy surface for the metal in Cu(I)-CusF is reported and compared with the one reported previously for Cu(I)-Atx1 (S. D. Dalosto, J. Phys. Chem. B, 111, 2932, 2007). The energetic to move the metal in both metallochaperones is remarkable similar. Whereas, for the Cu(I)-CusF(Trp-Gly) mutant, move the metal is 2 to 5 kcal/mol more costly than in the wide-type. A possible scenario for the copper translocation between CusF and other metallochaperon proteins is discussed.