In comparison, LsAA9 shows a high reaction barrier of 155 kJ/mol (126 kJ/mol for TPSS) with a reaction energy of -129 kJ/mol (-128 kJ/mol for TPSS). The reactant, transition Figure : Energy diagrams (in kJ/mol) for the reaction III for TaAA9 (left) and LsAA9 (right). The reactants 3 ′ and 3 for TaAA9 and LsAA9, respectively, were used as reference. Results were obtained for the triplet state with an extended QM region (see computational details). Results for the smaller QM region are provided in Table in the SI. state, and product structures are shown in Fig. (additional distances for chosen atoms are provided in Table in the SI). The transition states also display somewhat different bond-distances in the first coordination sphere to copper; the Cu-O Tyr distance varies from 2.9 in TaAA9 to 2.6 Å in LsAA9, highlighting that the otherwise quite similar active-site architectures may lead to different reactivity. As for reaction I, the de-protonation of tyrosine's OH-group leads to a decrease in the Cu-O Tyr175 distance of 0.2-0.3 Å in the product (2). We finally note that we decided to use 3 ′ for TaAA9 in Fig. and Fig. . This choice was made since we then have consistently small MM energies for the barrier (the reaction energy is less affected) as the QM region was enlarged for 3 ′ . We have not attempted to extend the QM region for 3, but based on the calculations with smaller QM region, the energy difference between 3 and 3 ′ for TaAA9 is sufficiently small so that none of the above conclusions change (see Table ). ). The structures were optimized using TPSS/def2-SV(P) while the energies given were obtained employing B3LYP/def2-TZVPP. Key distances are given in Å and energies in kJ/mol with reference to the reactant. Further bond distances for the different intermediates can be found in Table . Note that the structures were obtained with an extended QM region including Phe43 and Pro30 for TaAA9 and LsAA9, respectively.