Our calculations are anchored in the experimental geometry of four different LsAA9A crystal structures measured by Tandrup et al. (pdb codes 7PXI, 7PXV, 7PYI and 7PYD, see structures in blue boxes in Figure ). In the structures 7PXI and 7PXV no substrate is bound, and they will be labelled as Cu(II) and Cu(I) respectively. Cellotetraose is bound in the structures 7PYD and 7PYI, and they will be labelled Cu(II)-Cell-Cl -and Cu(I)-Cell-Cl -, respectively. Note that Tandrup et al. obtained the Cu(I) crystal structure (pdb code 7PXV) through chemical reduction with ascorbic acid, while the Cu(I)-Cell-Cl -structure (pdb code 7PYI) was photoreduced by increasing the radiation dose. Since all four crystal structures contain only non-hydrogen atoms, hydrogens were added with the program Maestro (which is part of the Schrödinger suite). From the resulting structures, we extracted the copper, the side chains of His1 and His78 (constituting the histidine brace), the side chains of His147, Gln162 and Tyr164, as well as any copper coordinating water molecules (labelled H2Oeq and H2Oax). Tyr164 is an axial ligand to the copper in AA9 and other LPMOs, while His147 and Gln162 are important residues in the second coordination sphere (see top left panel in Figure ). His1 is methylated 1 and the methylation was always kept. His147 was always protonated in the N ε2 position. From the crystal structures with the substrate, three units of the cellotetraose, the chloride anion and the so-called pocket water (labelled H2Opkt) were extracted additionally. The latter binds to the terminal NH2 group as described in Ref. . In the Cu(II) and Cu(I) structures without substrate, we further included a water molecule in a similar position to the pocket water (also labelled H2Opkt). In all extracted structures, His78, His147, Gln162 and Tyr164 were cut between C α and C β , while the N-terminal coordinating His1 was cut between the backbone carbon atom (C) and C α . Except for His1, only the side chain atoms of the residues were kept, and dangling bonds were saturated with hydrogen atoms. For the structures with cellotetraose, the three saccharide units closest to the copper centre were extracted, and the glycosidic bond was cut between the oxygen and the fourth saccharide unit. The resulting systems are shown in Figure and Figure (with optimized hydrogen positions, see below). The hydrogen positions were optimized with the quantum chemistry software ORCA 5.0.1 using the DFT functional TPSS and the def2-SV(P) basis set with D3 dispersion correction , Becke-Johnson damping and the resolution of identity (RI) approximation . The auxiliary basis set corresponding to def2-SV(P) was used for the RI approximation (def2/J). The positions of all non-hydrogen atoms were fixed at their crystal structure positions. All energies, orbitals, orbital energies and spin densities were obtained from single-point calculations on these structures with the DFT functionals B3LYP and a def2-TZVPP basis set. We use the default version of B3LYP in ORCA, where the calculation of Coulomb (J) and exchange (X) terms is done with the split RI-J and chain-ofspheres for exchange (RIJCOSX) approximation. We additionally calculated the orbital energies with the TPSS 66 functional. Since B3LYP and TPSS generally gave similar trends, we show only the B3LYP results in the main text and refer to Section S3 in the SI for the TPSS results.