LPMOs have a copper-containing active site with an N-terminal histidine (Proc. Nat. Acad. Sci., 2011). The active site was discovered in 2011 and is known as the histidine brace. LPMOs catalyse the oxidation of recalcitrant polysaccharides such as cellulose. Our current research interests involve understanding the catalytic mechanisms of these enzymes using a combination of structure, spectroscopy and theory, Nature Catalysis 2018.
In our most recent work with colleagues from Norway, we have used a combined NMR/EPR study to unravel the mechanism by which the activation of oxygen is coupled to the binding of substrates in LPMOs. We use an analysis of EPR hyperfine constants to show that the binding of chitin by LPMOs is accompanied by a shift in the coordination geometry at the copper ion.
Figure: Changes in the active site structure of chitin-active LPMOs upon binding of substrate.
How do LPMOs interact with their natural polysaccharide substrates? This is a difficult question to answer since the solid/heterogeneous nature of the substrate precludes use of many of the normal techniques for the study of enzymes. To overcome this limitation we have recently used EPR spectroscopy to study LPMOs bound to cellulose fibres extracted from celery. These fibres are an excellent source of uniaxially-orientated cellulose, thus permitting the use of orientation-dependent EPR spectroscopy to give information on how LPMOs interact with their natural substrate. This work is published in Dalton Transactions.
Figure: interaction of LsAA9 LPMO with single cellulose fibril.
- Mechanistic basis of substrate-O2 coupling within a chitin-active lytic polysaccharide monooxygenase: an integrated NMR/EPR study, G Courtade, L Ciano, A Paradisi, P J Lindley, Z Forsberg, M Sorlie, R Wimmer, G J Davies, V G H Eijsink, P H Walton, F L Aachmann, Proc. Nat. Acad. Sci. 2020, 117(32), 19178-19189 (open access article).
- A fungal family of lytic polysaccharide monooxygenase-like copper proteins, A Labourel, K Frandsen, F Zhang, N Brouilly, S Grisel, M Haon, L Ciano, D Ropartz, M Fanuel, F Martin, D Navarro, M-N Rosso, T Tandrup, B Bissaro, K Johansen, A Zerva, P H Walton, B Henrissat, L Leggio, J-G Berrin, Nature Chem. Biol. 2020, 16, 345-350.
- Formation of a copper(II)-tyrosyl complex at the active site of lytic polysaccharide monooxygenases following oxidation by H2O2, A Paradisi, E M Johnston, M Tovborg, C R Nicoll, L Ciano, A Dowle, J McMaster, Y Hancock, G J Davies, P H Walton, J. Am. Chem. Soc., 2019, 141, 18585-18599 (open access article).
- Bracing copper for the oxidation of C-H bonds, L Ciano, G J Davies, W B Tolman, P H Walton Nature Catalysis, 2018, 1(8), 571-577.
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.
He is the recipient of multiple national* and international** awards, including:
He has also been Editor of Dalton Transactions (2004-2008), chair of Heads of Chemistry UK, chair of the Royal Society of Chemistry's Diversity Committee, was named as a 'Person of Influence' by the University of Toronto's Women in Chemistry Group and is one the RSC's 175 Faces of Chemistry. Paul is an internationally-known advocate of equality in sciences and lectures widely on the subject.