The role of the active site tyrosine in the mechanism of lytic polysaccharide monooxygenase
(2021) In Chemical Science 12(1). p.352-362- Abstract
Catalytic breakdown of polysaccharides can be achieved more efficiently by means of the enzymes lytic polysaccharide monooxygenases (LPMOs). However, the LPMO mechanism has remained controversial, preventing full exploitation of their potential. One of the controversies has centered around an active site tyrosine, present in most LPMO classes. Recent investigations have for the first time obtained direct (spectroscopic) evidence for the possibility of chemical modification of this tyrosine. However, the spectroscopic features obtained in the different investigations are remarkably different, with absorption maximum at 420 and 490 nm, respectively. In this paper we use density functional theory (DFT) in a QM/MM formulation to reconcile... (More)
Catalytic breakdown of polysaccharides can be achieved more efficiently by means of the enzymes lytic polysaccharide monooxygenases (LPMOs). However, the LPMO mechanism has remained controversial, preventing full exploitation of their potential. One of the controversies has centered around an active site tyrosine, present in most LPMO classes. Recent investigations have for the first time obtained direct (spectroscopic) evidence for the possibility of chemical modification of this tyrosine. However, the spectroscopic features obtained in the different investigations are remarkably different, with absorption maximum at 420 and 490 nm, respectively. In this paper we use density functional theory (DFT) in a QM/MM formulation to reconcile these (apparently) conflicting results. By modeling the spectroscopy as well as the underlying reaction mechanism we can show how formation of two isomers (both involving deprotonation of tyrosine) explains the difference in the observed spectroscopic features. Both isomers have a [TyrO-Cu-OH]+ moiety with the OH in either the cis- or trans-position to a deprotonated tyrosine. Although the cis-[TyrO-Cu-OH]+ moiety is well positioned for oxidation of the substrate, preliminary calculations with the substrate reveal that the reactivity is at best moderate, making a protective role of tyrosine more likely.
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- author
- Mcevoy, Aina ; Creutzberg, Joel LU ; Singh, Raushan K. ; Bjerrum, Morten J. and Hedegård, Erik D. LU
- organization
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Chemical Science
- volume
- 12
- issue
- 1
- pages
- 11 pages
- publisher
- Royal Society of Chemistry
- external identifiers
-
- scopus:85099120646
- pmid:34163601
- ISSN
- 2041-6520
- DOI
- 10.1039/d0sc05262k
- language
- English
- LU publication?
- yes
- id
- 3312c52e-39fc-47ba-9093-6ae01d163694
- date added to LUP
- 2021-01-19 11:42:26
- date last changed
- 2024-06-27 07:10:03
@article{3312c52e-39fc-47ba-9093-6ae01d163694,
abstract = {{<p>Catalytic breakdown of polysaccharides can be achieved more efficiently by means of the enzymes lytic polysaccharide monooxygenases (LPMOs). However, the LPMO mechanism has remained controversial, preventing full exploitation of their potential. One of the controversies has centered around an active site tyrosine, present in most LPMO classes. Recent investigations have for the first time obtained direct (spectroscopic) evidence for the possibility of chemical modification of this tyrosine. However, the spectroscopic features obtained in the different investigations are remarkably different, with absorption maximum at 420 and 490 nm, respectively. In this paper we use density functional theory (DFT) in a QM/MM formulation to reconcile these (apparently) conflicting results. By modeling the spectroscopy as well as the underlying reaction mechanism we can show how formation of two isomers (both involving deprotonation of tyrosine) explains the difference in the observed spectroscopic features. Both isomers have a [TyrO-Cu-OH]+ moiety with the OH in either the cis- or trans-position to a deprotonated tyrosine. Although the cis-[TyrO-Cu-OH]+ moiety is well positioned for oxidation of the substrate, preliminary calculations with the substrate reveal that the reactivity is at best moderate, making a protective role of tyrosine more likely.</p>}},
author = {{Mcevoy, Aina and Creutzberg, Joel and Singh, Raushan K. and Bjerrum, Morten J. and Hedegård, Erik D.}},
issn = {{2041-6520}},
language = {{eng}},
number = {{1}},
pages = {{352--362}},
publisher = {{Royal Society of Chemistry}},
series = {{Chemical Science}},
title = {{The role of the active site tyrosine in the mechanism of lytic polysaccharide monooxygenase}},
url = {{http://dx.doi.org/10.1039/d0sc05262k}},
doi = {{10.1039/d0sc05262k}},
volume = {{12}},
year = {{2021}},
}