About the Seminar
The active sites of copper oxygenases and their reactivity with H2O2
Lytic polysaccharide monooxygenases (LPMOs) are relatively recently discovered enzymes that catalyse the oxidation of polysaccharides, leading to chain cleavage. LPMOs has transformed our understanding of biomass degradation, and—moreover—are now critical components in the enzymatic breakdown of biomass in the second generation bioethanol industry.1 We and others have also recently shown that LPMOs are key virulence factors in major plant diseases.2
Our recent work has concentrated on the discovery of new LPMO active sites, some of which will be described in the seminar.. We have also examined the action of oxidizing agents on the enzyme which has been shown to enhance the activity of the enzymes on saccharidic substrates, but also lead to rapid inactivation of the enzyme, presumably through protein oxidation.3
Active site structure of an LPMO and oxidized amino acids (red) following treatment with H2O2.
In this talk, in addition to a description of the structure and reactivity of LPMOs, I will show that the use of UV/vis, CD, XAS, EPR, MCD, MS and resonance Raman spectroscopies augmented with DFT calculations, reveals that one of the products of protein oxidation in an AA9 LPMO is a long-lived ground-state singlet Cu(II)-tyrosyl species, which is inactive for the oxidation of saccharidic substrates. I will also show that this state evolves from an intermediate Cu(II)…tyrosyl triplet species via a open-shell singlet Cu(II)…histidyl radical.
- K. E. H. Frandsen, P. H. Walton et al, Nature Chem. Biol. 298—303 (2016).
- F. Sabbadin, P. H. Walton et al, Science, 373, 774-779 (2021).
- A. Paradisi, P. H. Walton et al, J. Am. Chem. Soc. 18585—18599 (2019).
About the Speaker
Paul Walton obtained his PhD in 1990 (University of Nottingham, UK), followed by two years as a NATO/SERC postdoctoral fellow at the University of California, Berkeley, USA. He joined the Department of Chemistry at York as a faculty member in 1993. Between 2004 and 2010 he was chair of department. His main research area is bioinorganic chemistry, in which he has made contributions to the understanding of copper oxidases, including the discovery of the histidine brace.