A frontier-orbital view of the initial steps of lytic polysaccharide monooxygenase reactions
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
A frontier-orbital view of the initial steps of lytic polysaccharide monooxygenase reactions. / Wieduwilt, Erna Katharina; Lo Leggio, Leila; Hedegård, Erik Donovan.
I: Dalton Transactions (Online), Bind 53, Nr. 13, 2024, s. 5796-5807.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - A frontier-orbital view of the initial steps of lytic polysaccharide monooxygenase reactions
AU - Wieduwilt, Erna Katharina
AU - Lo Leggio, Leila
AU - Hedegård, Erik Donovan
PY - 2024
Y1 - 2024
N2 - Lytic polysaccharide monooxygenases (LPMOs) are copper enzymes that oxidatively cleave the strong C-H bonds in recalcitrant polysaccharide substrates, thereby playing a crucial role in biomass degradation. Recently, LPMOs have also been shown to be important for several pathogens. It is well established that the Cu(II) resting state of LPMOs is inactive, and the electronic structure of the active site needs to be altered to transform the enzyme into an active form. Whether this transformation occurs due to substrate binding or due to a unique priming reduction has remained speculative. Starting from four different crystal structures of the LPMO LsAA9A with well-defined oxidation states, we use a frontier molecular orbital approach to elucidate the initial steps of the LPMO reaction. We give an explanation for the requirement of the unique priming reduction and analyse electronic structure changes upon substrate binding. We further investigate how the presence of the substrate could facilitate an electron transfer from the copper active site to an H2O2 co-substrate. Our findings could help to control experimental LPMO reactions.
AB - Lytic polysaccharide monooxygenases (LPMOs) are copper enzymes that oxidatively cleave the strong C-H bonds in recalcitrant polysaccharide substrates, thereby playing a crucial role in biomass degradation. Recently, LPMOs have also been shown to be important for several pathogens. It is well established that the Cu(II) resting state of LPMOs is inactive, and the electronic structure of the active site needs to be altered to transform the enzyme into an active form. Whether this transformation occurs due to substrate binding or due to a unique priming reduction has remained speculative. Starting from four different crystal structures of the LPMO LsAA9A with well-defined oxidation states, we use a frontier molecular orbital approach to elucidate the initial steps of the LPMO reaction. We give an explanation for the requirement of the unique priming reduction and analyse electronic structure changes upon substrate binding. We further investigate how the presence of the substrate could facilitate an electron transfer from the copper active site to an H2O2 co-substrate. Our findings could help to control experimental LPMO reactions.
KW - Mixed Function Oxygenases/chemistry
KW - Hydrogen Peroxide
KW - Copper/chemistry
KW - Polysaccharides/metabolism
KW - Oxidation-Reduction
U2 - 10.1039/d3dt04275h
DO - 10.1039/d3dt04275h
M3 - Journal article
C2 - 38445349
VL - 53
SP - 5796
EP - 5807
JO - Dalton Transactions (Online)
JF - Dalton Transactions (Online)
SN - 1477-9234
IS - 13
ER -
ID: 389361687