Lytic polysaccharide monooxygenase (LPMO) enzymes have attracted considerable
attention due to their ability to enhance polysaccharide depolymerization,
making them interesting in respect to production of biofuel from cellulose. The
LPMOs are metalloenzymes that contain a mononuclear copper active site that can
active dioxygen. However, many details of this activation are unclear, and have
previously been investigated from a computational angle. Yet, these studies
have either employed only molecular mechanics (MM), which are inaccurate for
metal active sites, or they have described only the active site with quantum
mechanics (QM) and neglected the effect of the protein. Here, we employ hybrid
QM and MM (QM/MM) methods to investigate the first steps of the LPMO mechanism,
which is reduction of of Cu(II) to Cu(I) and formation of a Cu(II)-superoxide
complex. In the latter complex, the superoxide can bind either in an equatorial
or an axial position. For both steps we obtain structures that are markedly
different from previous suggestions, based on vacuum calculations. Our
calculations show that the equatorial isomer of the superoxide complex is over
60 kJ/mol more stable than the axial isomer, being stabilized by interactions
with a second-coordination-sphere Gln residue, showing a possible role for this
residue. Coordination of superoxide in this manner is in agreement with recent
experimental suggestions.Comment: 21 pages, 6 figures, 3 tables. 20 pages Supporting Informatio
