Histidine oxidation in lytic polysaccharide monooxygenase.

Autor: Torbjörnsson M; Department of Theoretical Chemistry, Lund University, Chemical Centre, P. O. Box 124, 221 00, Lund, Sweden., Hagemann MM; Department of Physics, Chemistry, and Pharmacy, University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark., Ryde U; Department of Theoretical Chemistry, Lund University, Chemical Centre, P. O. Box 124, 221 00, Lund, Sweden. Ulf.Ryde@teokem.lu.se., Hedegård ED; Department of Theoretical Chemistry, Lund University, Chemical Centre, P. O. Box 124, 221 00, Lund, Sweden. erdh@sdu.dk.; Department of Physics, Chemistry, and Pharmacy, University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark. erdh@sdu.dk.
Jazyk: angličtina
Zdroj: Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry [J Biol Inorg Chem] 2023 Apr; Vol. 28 (3), pp. 317-328. Date of Electronic Publication: 2023 Feb 25.
DOI: 10.1007/s00775-023-01993-4
Abstrakt: The lytic polysaccharide monooxygenases (LPMOs) comprise a super-family of copper enzymes that boost the depolymerisation of polysaccharides by oxidatively disrupting the glycosidic bonds connecting the sugar units. Industrial use of LPMOs for cellulose depolymerisation has already begun but is still far from reaching its full potential. One issue is that the LPMOs self-oxidise and thereby deactivate. The mechanism of this self-oxidation is unknown, but histidine residues coordinating to the copper atom are the most susceptible. An unusual methyl modification of the NE2 atom in one of the coordinating histidine residues has been proposed to have a protective role. Furthermore, substrate binding is also known to reduce oxidative damage. We here for the first time investigate the mechanism of histidine oxidation with combined quantum and molecular mechanical (QM/MM) calculations, with outset in intermediates previously shown to form from a reaction with peroxide and a reduced LPMO. We show that an intermediate with a [Cu-O] + moiety is sufficiently potent to oxidise the nearest C-H bond on both histidine residues, but methylation of the NE2 atom of His-1 increases the reaction barrier of this reaction. The substrate further increases the activation barrier. We also investigate a [Cu-OH] 2+ intermediate with a deprotonated tyrosine radical. This intermediate was previously proposed to have a protective role, and we also find it to have higher barriers than the corresponding a [Cu-O] + intermediate.
(© 2023. The Author(s).)
Databáze: MEDLINE
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