Density functional theory (DFT/BP86) and the polarized continuum model (PCM/epsilon = 20) have been applied to perform calculations for the A-cluster of acetyl-CoA synthase enzyme. The geometry optimization was carried out for the oxidized, one- and two-electron reduced A-cluster as well as for A-cluster with ligands important in the catalytic cycle, i.e., H2O, CO, CH3, OH-, and H+. The electronic structure of the studied species (spin densities and NBO charges) was analyzed and the metal-metal interactions were investigated with the use of Wiberg bond indices (WBIs). The pK(a) values and the reduction potentials have been determined. On the basis of the calculations, the mechanism of PCET reductive activation of the A-cluster has been proposed for the methylation catalytic step.