Oxygen Activation at the Active Site of a Fungal Lytic Polysaccharide Monooxygenase

Angew Chem Int Ed Engl. 2017 Jan 16;56(3):767-770. doi: 10.1002/anie.201610502. Epub 2016 Dec 22.


Lytic polysaccharide monooxygenases have attracted vast attention owing to their abilities to disrupt glycosidic bonds via oxidation instead of hydrolysis and to enhance enzymatic digestion of recalcitrant substrates including chitin and cellulose. We have determined high-resolution X-ray crystal structures of an enzyme from Neurospora crassa in the resting state and of a copper(II) dioxo intermediate complex formed in the absence of substrate. X-ray crystal structures also revealed "pre-bound" molecular oxygen adjacent to the active site. An examination of protonation states enabled by neutron crystallography and density functional theory calculations identified a role for a conserved histidine in promoting oxygen activation. These results provide a new structural description of oxygen activation by substrate free lytic polysaccharide monooxygenases and provide insights that can be extended to reactivity in the enzyme-substrate complex.

Keywords: copper; oxidoreductases; oxygen activation; polysaccharide monooxygenases; protein structures.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Catalytic Domain
  • Mixed Function Oxygenases / chemistry
  • Mixed Function Oxygenases / metabolism*
  • Models, Molecular
  • Neurospora crassa / enzymology*
  • Oxygen / chemistry
  • Oxygen / metabolism*
  • Polysaccharides / chemistry
  • Polysaccharides / metabolism*


  • Polysaccharides
  • Mixed Function Oxygenases
  • Oxygen