Fine Tuning of the Copper Active Site in Polysaccharide Monooxygenases

Type-2 copper active site, one of several important copper active sites in biology, was recently found in the novel superfamily of polysaccharide monooxygenases (PMOs) that cleave recalcitrant polysaccharides via an unprecedented oxidative mechanism. The copper center in PMOs is ligated by the bidentate N-terminal histidine residue and another conserved histidine residue, forming a unique T-shaped core termed as Histidine brace. This core serves as the foundation for diverse structures and electronic properties among PMO families and sub-families. Understanding of the copper active site in PMOs is limited to the static solid structures obtained with XRD, while in several families the copper center exists as a mixture of species in solution as indicated by electron paramagnetic resonance (EPR) spectroscopy. To obtain further details on the copper active site in PMOs, we carried out DFT calculations and MD simulations on MtPMO3* that were previously studied with XRD, EPR, mutagenesis, and activity assays. R...