Mechanism of hydrogen peroxide formation by lytic polysaccharide monooxygenase.
Octav CaldararuEsko OksanenUlf RydeErik Donovan HedegårdPublished in: Chemical science (2018)
Lytic polysaccharide monooxygenases (LPMOs) are copper-containing metalloenzymes that can cleave the glycosidic link in polysaccharides. This could become crucial for production of energy-efficient biofuels from recalcitrant polysaccharides. Although LPMOs are considered oxygenases, recent investigations have shown that H2O2 can also act as a co-substrate for LPMOs. Intriguingly, LPMOs generate H2O2 in the absence of a polysaccharide substrate. Here, we elucidate a new mechanism for H2O2 generation starting from an AA10-LPMO crystal structure with an oxygen species bound, using QM/MM calculations. The reduction level and protonation state of this oxygen-bound intermediate has been unclear. However, this information is crucial to the mechanism. We therefore investigate the oxygen-bound intermediate with quantum refinement (crystallographic refinement enhanced with QM calculations), against both X-ray and neutron data. Quantum refinement calculations suggest a Cu(ii)-O-2 system in the active site of the AA10-LPMO and a neutral protonated -NH2 state for the terminal nitrogen atom, the latter in contrast to the original interpretation. Our QM/MM calculations show that H2O2 generation is possible only from a Cu(i) center and that the most favourable reaction pathway is to involve a nearby glutamate residue, adding two electrons and two protons to the Cu(ii)-O-2 system, followed by dissociation of H2O2.
Keyphrases
- molecular dynamics
- density functional theory
- hydrogen peroxide
- monte carlo
- crystal structure
- molecular dynamics simulations
- water soluble
- nitric oxide
- metal organic framework
- aqueous solution
- electron transfer
- amino acid
- machine learning
- health information
- computed tomography
- contrast enhanced
- quantum dots
- deep learning