described above. The Cu(I)-Cell…H2O2 structure is shown in Figure . Instead of obtaining a pre-bound Cu(I)…H2O2 (i.e. the structure without substrate) with the procedure described above, we could only obtain a structure reminiscent of the "caged" state (indicated as Cu(II)-HO--OH in Figure ), where H2O2 coordinates to copper and the O-O distance is elongated to distances of approximately 2 or more Ångström. The prebound form has previously been calculated with both TPSS and B3LYP using a QM/MM embedding scheme to mimic the protein environment and it was also obtained by Lim et al. who employed a QM-cluster approach. Therefore, we optimized the Cu(I)…H2O2 structure with the same functional (B3LYP) that Lim ). Right: Structures with pre-bound H2O2 (see products of reactions 5a and 5b in Figure ) derived from replacing water or chloride in the two crystal structures of LsAA9A with oxidation state I. Description of the geometry: The active site of LPMOs consists of a copper center coordinated by two histidines (His1 and His78), forming the histidine brace. His1 is the N-terminal residue that binds bidentate through the amine of the N-terminus and the imidazole side chain. His78 binds only through the side chain. In LPMOs of fungal origin, His1 is often methylated (this is also the case for LsAA9). Apart from the histidine brace, there are no residues that are strictly conserved across all LPMOs, however, many LPMOs have a generally conserved tyrosine (Tyr164 in LsAA9) as axial ligand in the oxidation state II. Two water ligands (one in axial and one in equatorial position) complete the octahedral Jahn-Teller distorted active site with axially elongated ligands. In the second coordination sphere, we included Gln162 and His147, which are both important in stabilizing the pre-bound H2O2 structures. If cellotetraose is present, it binds from subsite -2 to +2, and forms a hydrogen bond to the so-called "pocket water" 11 that in turn hydrogen bonds to the terminal NH2 group of His1. Geometrical changes upon reduction and substrate binding are described in the main text and in detail in Ref. .