Several open questions now remain concerning the initial parts of the hole-hopping mechanism: (i) How does the tyrosine radical formation compare energetically, relative to the histidyl radical formation? (ii) Are both tyrosyl and histidyl radicals part of the protective mechanism? (iii) Do different LPMOs display different mechanisms? The last open question arises since previous QM/MM calculations on the protective or oxidative damage mechanisms focused exclusively on a particular member of the AA9 family, namely LsAA9, whereas experimental studies focused on different LPMOs In this paper we will address (i) and (ii) by employing QM/MM calculations for reactions I-III in Fig. . We will also address (iii) by, for the first time, directly comparing oxidative damage and protective mechanisms of two enzymes, namely LsAA9 and TaAA9 (see Fig. ). One of our findings is that LsAA9 and TaAA9 (that have quite similar second coordination spheres) occasionally display significant differences in their mechanisms. Given that little is known concerning the initial events of these protective mechanisms, our findings are likely to be highly relevant for other oxoreductases as well.