Three-dimensional structural diversity (conformational diversity) of glycans is essential for their biological functions. Molecular dynamics (MD) simulations provide insight into the three-dimensional (3D-) structures of biomolecules in atomic resolution which are difficult to obtain by experiment. However, their highly complex and flexible structures make glycans difficult to simulate. This minireview summarizes recent challenges in MD simulations of glycans using enhanced sampling techniques. Using MD simulations, various 3D-structures are revealed at atomic resolution, not only for isolated glycans but also for glycoconjugates and glycan-bound complexes. The role of MD simulations is not limited for interpretation of experimental results. The simulations are used to predict experiments, leading the integrated computational and experimental studies on the structure-function relationship of glycans. We hope that this article will help prompt various integrated studies of glycans in the future.

The cell wall is the outermost layer of the fungal cell. The fungal cell wall, which is primarily composed of polysaccharides, is a structure that plays important roles in proliferation and morphogenesis, which are essential for the survival of fungi. Furthermore, the molecular patterns of these cell wall polysaccharides are unique to fungi; accordingly, these biopolymers are used as molecular targets in the development of antimycotic drugs with minimal adverse effects. Nonetheless, the fact that the biosynthetic pathways and mechanisms by which fungal cell walls are constructed remain unclear is a barrier to the rational design of antimycotics. This review is focused on the biosynthesis of 1,6-branched β-(1,3)-glucan, the polysaccharide that constitutes the core structure of fungal cell walls.

Glycosaminoglycans (GAGs), including chondroitin sulfate, dermatan sulfate, heparan sulfate, and hyaluronan, are ubiquitously present on animal cell surfaces as well as in the extracellular matrix, and they are involved in various biological events, such as cell adhesion, regulation of cell signaling, and construction of extracellular matrix. Most GAGs are internalized into cells by endocytosis and depolymerized into monosaccharides by endo- and exo-type enzymes of endosomes and lysosomes. A part of GAGs is also degraded extracellularly, which may be involved in the regulation of their functions. Mucopolysaccharidoses are caused by a deficiency of exo-type GAG-degrading enzymes. Although some hereditary diseases are considered to be involved in mutations in the genes coding endo-type GAG-degrading enzymes, the physiological mechanisms remain to be clarified. The frequency of mucopolysaccharidoses is higher than that of other GAG-related genetic diseases. Since mucopolysaccharidoses have been investigated for a long time, the methods to treat them have been established to some extent. However, there are several problems to be overcome to realize effective treatments. In this review, hereditary diseases caused by abnormality of GAG-catabolism are outlined from the standpoint of glycobiology.

The group of filamentous fungi called wood rotting fungi comprises the main decomposers of woody biomass in forest ecosystems. These wood rotting fungi secrete various extracellular enzymes, such as cellulases and lytic polysaccharide monooxygenases (LPMOs) to degrade cellulose in wood cell walls. Interestingly, one particular group of wood-rotting fungi, called brown-rot fungi, lacks key cellulases for degrading crystalline cellulose, namely cellobiohydrolases (CBHs), with only a few exceptions. On the other hand, genes encoding LPMOs are widely conserved among brown-rot fungi, suggesting the importance of these enzymes in the brown-rot system. In this paper, after reviewing the wood degradation process by wood rotting fungi, we describe the history of the discovery of LPMOs and then review current knowledge on the characteristics of these enzymes. We then review our research on LPMOs derived from a brown-rot fungus and discuss possible physiological roles of LPMOs in the brown-rot system. Finally, we address the significance of LPMOs in the evolution of brown-rot system.

Three-dimensional structural diversity (conformational diversity) of glycans is essential for their biological functions. Molecular dynamics (MD) simulations provide insight into the three-dimensional (3D-) structures of biomolecules in atomic resolution which are difficult to obtain by experiment. However, their highly complex and flexible structures make glycans difficult to simulate. This minireview summarizes recent challenges in MD simulations of glycans using enhanced sampling techniques. Using MD simulations, various 3D-structures are revealed at atomic resolution, not only for isolated glycans but also for glycoconjugates and glycan-bound complexes. The role of MD simulations is not limited for interpretation of experimental results. The simulations are used to predict experiments, leading the integrated computational and experimental studies on the structure-function relationship of glycans. We hope that this article will help prompt various integrated studies of glycans in the future.

The cell wall is the outermost layer of the fungal cell. The fungal cell wall, which is primarily composed of polysaccharides, is a structure that plays important roles in proliferation and morphogenesis, which are essential for the survival of fungi. Furthermore, the molecular patterns of these cell wall polysaccharides are unique to fungi; accordingly, these biopolymers are used as molecular targets in the development of antimycotic drugs with minimal adverse effects. Nonetheless, the fact that the biosynthetic pathways and mechanisms by which fungal cell walls are constructed remain unclear is a barrier to the rational design of antimycotics. This review is focused on the biosynthesis of 1,6-branched β-(1,3)-glucan, the polysaccharide that constitutes the core structure of fungal cell walls.

Glycosaminoglycans (GAGs), including chondroitin sulfate, dermatan sulfate, heparan sulfate, and hyaluronan, are ubiquitously present on animal cell surfaces as well as in the extracellular matrix, and they are involved in various biological events, such as cell adhesion, regulation of cell signaling, and construction of extracellular matrix. Most GAGs are internalized into cells by endocytosis and depolymerized into monosaccharides by endo- and exo-type enzymes of endosomes and lysosomes. A part of GAGs is also degraded extracellularly, which may be involved in the regulation of their functions. Mucopolysaccharidoses are caused by a deficiency of exo-type GAG-degrading enzymes. Although some hereditary diseases are considered to be involved in mutations in the genes coding endo-type GAG-degrading enzymes, the physiological mechanisms remain to be clarified. The frequency of mucopolysaccharidoses is higher than that of other GAG-related genetic diseases. Since mucopolysaccharidoses have been investigated for a long time, the methods to treat them have been established to some extent. However, there are several problems to be overcome to realize effective treatments. In this review, hereditary diseases caused by abnormality of GAG-catabolism are outlined from the standpoint of glycobiology.

The group of filamentous fungi called wood rotting fungi comprises the main decomposers of woody biomass in forest ecosystems. These wood rotting fungi secrete various extracellular enzymes, such as cellulases and lytic polysaccharide monooxygenases (LPMOs) to degrade cellulose in wood cell walls. Interestingly, one particular group of wood-rotting fungi, called brown-rot fungi, lacks key cellulases for degrading crystalline cellulose, namely cellobiohydrolases (CBHs), with only a few exceptions. On the other hand, genes encoding LPMOs are widely conserved among brown-rot fungi, suggesting the importance of these enzymes in the brown-rot system. In this paper, after reviewing the wood degradation process by wood rotting fungi, we describe the history of the discovery of LPMOs and then review current knowledge on the characteristics of these enzymes. We then review our research on LPMOs derived from a brown-rot fungus and discuss possible physiological roles of LPMOs in the brown-rot system. Finally, we address the significance of LPMOs in the evolution of brown-rot system.