Copper coordination to the putative cell binding site of angiogenin: a DFT investigation

We present a DFT study of the structural and spectroscopic properties of the complex formed by Cu2? with the peptide fragment Ac-PHREN-NH2, which encompasses the putative cell binding domain of angiogenin, as well as with its Ac-PHRQN-NH2 variant. Analysis of structures, energies and spectroscopic parameters has allowed to conclude that the metal coordination environment at pH 8 is formed by a nitrogen atom of His, two deprotonated amide groups, and an oxygen atom from the COO- side chain of Glu, in nice agreement with recent experimental results (La Mendola et al. in Dalton Trans, 39:10678, 2010). Moreover, DFT results allowed to reveal that the Glu side chain of the Ac-PHREN-NH2 peptide is coordinated in equatorial position, in a tetrahedrically distorted square planar arrangement, fully disclosing the effects of Cu2? binding on the structural properties of this key angiogenin portion. In the Ac-PHRQN-NH2 variant, the carboxylate group is replaced by a H2O molecule in a coordination arrangement similar to that of the wild-type system.