Having established the effect of the priming electron on the frontier orbitals, we next analyse the influence of substrate binding (corresponding to reactions 2a and 2b in Figure ), comparing the Cu(II) and Cu(II)-Cell structures as well as the Cu(I) and Cu(I)-Cell structures shown in Figure . Tandrup et al. report two correlated changes to the active site geometries upon substrate binding: First, binding of the substrates induced a loss of planarity in the copper and the equatorial ligands that are almost coplanar in the Cu(II) structure without substrate. Second, the distance between copper and tyrosine was reduced by ca. 0.2 Å upon binding of the substrate to the Cu(II) structure (according to reaction 1b in Figure , see Table for distances). A third change already described by Frandsen et al. is that the axial water molecule is displaced by a hydroxymethyl group of the substrate (see Figure ). In the following, we will describe how these structural changes influence the electronic structure.