The role of the active site tyrosine in the mechanism of lytic polysaccharide monooxygenase

Aina McEvoy, Joel Creutzberg, Raushan K. Singh, Morten J. Bjerrum, Erik D. Hedegård*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

1 Downloads (Pure)

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 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.
Original languageEnglish
JournalChemical Science
Volume12
Pages (from-to)352–362
ISSN2041-6520
DOIs
Publication statusPublished - 2021
Externally publishedYes

Fingerprint Dive into the research topics of 'The role of the active site tyrosine in the mechanism of lytic polysaccharide monooxygenase'. Together they form a unique fingerprint.

Cite this