Histidine oxidation in lytic polysaccharide monooxygenase
Torbjörnsson, Magne LU ; Hagemann, Marlisa M. LU ; Ryde, Ulf LU
and Hedegård, Erik Donovan
LU
(2023)
In Journal of Biological Inorganic Chemistry
28(3).
p.317-328
- Abstract
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.... (More)
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.
(Less)
- author
- Torbjörnsson, Magne
LU
; Hagemann, Marlisa M.
LU
; Ryde, Ulf
LU
and Hedegård, Erik Donovan
LU
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Histidine methylation, Histidine oxidation, Lytic polysaccharide monooxygenase, QM/MM
- in
- Journal of Biological Inorganic Chemistry
- volume
- 28
- issue
- 3
- pages
- 12 pages
- publisher
- Springer
- external identifiers
-
- scopus:85148573997
- pmid:36828975
- ISSN
- 0949-8257
- DOI
- 10.1007/s00775-023-01993-4
- language
- English
- LU publication?
- yes
- id
- cd78177b-f0f8-4c2b-977f-a18349e99237
- date added to LUP
- 2023-03-13 14:42:58
- date last changed
- 2024-06-14 00:33:36
@article{cd78177b-f0f8-4c2b-977f-a18349e99237,
abstract = {{<p>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]<sup>+</sup> 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]<sup>2+</sup> 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]<sup>+</sup> intermediate. <br/></p>}},
author = {{Torbjörnsson, Magne and Hagemann, Marlisa M. and Ryde, Ulf and Hedegård, Erik Donovan}},
issn = {{0949-8257}},
keywords = {{Histidine methylation; Histidine oxidation; Lytic polysaccharide monooxygenase; QM/MM}},
language = {{eng}},
number = {{3}},
pages = {{317--328}},
publisher = {{Springer}},
series = {{Journal of Biological Inorganic Chemistry}},
title = {{Histidine oxidation in lytic polysaccharide monooxygenase}},
url = {{http://dx.doi.org/10.1007/s00775-023-01993-4}},
doi = {{10.1007/s00775-023-01993-4}},
volume = {{28}},
year = {{2023}},
}