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On the impact of carbohydrate-binding modules (CBMs) in lytic polysaccharide monooxygenases (LPMOs).

ABSTRACT: Lytic polysaccharide monooxygenases (LPMOs) have revolutionized our understanding of how enzymes degrade insoluble polysaccharides. Compared with the substantial knowledge developed on the structure and mode of action of the catalytic LPMO domains, the (multi)modularity of LPMOs has received less attention. The presence of other domains, in particular carbohydrate-binding modules (CBMs), tethered to LPMOs has profound implications for the catalytic performance of the full-length enzymes. In the last few years, studies on LPMO modularity have led to advancements in elucidating how CBMs, other domains, and linker regions influence LPMO structure and function. This mini review summarizes recent literature, with particular focus on comparative truncation studies, to provide an overview of the diversity in LPMO modularity and the functional implications of this diversity.

SUBMITTER: Forsberg Z

PROVIDER: S-EPMC10154629 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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On the impact of carbohydrate-binding modules (CBMs) in lytic polysaccharide monooxygenases (LPMOs).

Forsberg Zarah Z Courtade Gaston G

Essays in biochemistry 20230401 3

Lytic polysaccharide monooxygenases (LPMOs) have revolutionized our understanding of how enzymes degrade insoluble polysaccharides. Compared with the substantial knowledge developed on the structure and mode of action of the catalytic LPMO domains, the (multi)modularity of LPMOs has received less attention. The presence of other domains, in particular carbohydrate-binding modules (CBMs), tethered to LPMOs has profound implications for the catalytic performance of the full-length enzymes. In the ...[more]

PMID: 36504118

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Project description:The lytic polysaccharide monooxygenases (LPMOs) are copper metalloenzymes that can enhance polysaccharide depolymerization through an oxidative mechanism and hence boost generation of biofuel from e.g. cellulose. By employing density functional theory in a combination of quantum mechanics and molecular mechanics (QM/MM), we report a complete description of the molecular mechanism of LPMOs. The QM/MM scheme allows us to describe all reaction steps with a detailed protein environment and we show that this is necessary. Several active species capable of abstracting a hydrogen from the substrate have been proposed previously and starting from recent crystallographic work on a substrate-LPMO complex, we investigate previously suggested paths as well as new ones. We describe the generation of the reactive intermediates, the abstraction of a hydrogen atom from the polysaccharide substrate, as well as the final recombination step in which OH is transferred back to the substrate. We show that a superoxo [CuO2]+ complex can be protonated by a nearby histidine residue (suggested by recent mutagenesis studies and crystallographic work) and, provided an electron source is available, leads to formation of an oxyl-complex after cleavage of the O-O bond and dissociation of water. The oxyl complex either reacts with the substrate or is further protonated to a hydroxyl complex. Both the oxyl and hydroxyl complexes are also readily generated from a reaction with H2O2, which was recently suggested to be the true co-substrate, rather than O2. The C-H abstraction by the oxyl and hydroxy complexes is overall favorable with activation barriers of 69 and 94 kJ mol-1, compared to the much higher barrier (156 kJ mol-1) obtained for the copper-superoxo species. We obtain good structural agreement for intermediates for which structural data are available and the estimated reaction energies agree with experimental rate constants. Thus, our suggested mechanism is the most complete to date and concur with available experimental evidence.

Dataset Information

On the impact of carbohydrate-binding modules (CBMs) in lytic polysaccharide monooxygenases (LPMOs).

Publications

On the impact of carbohydrate-binding modules (CBMs) in lytic polysaccharide monooxygenases (LPMOs).

Similar Datasets

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