K. Fukase - Academia.edu (original) (raw)

Papers by K. Fukase

ChemInform, 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Journal of Clinical Investigation, 2000

iScience

The structural basis of sialoglycans recognition by h/m CD22 has been investigated The binding mo... more The structural basis of sialoglycans recognition by h/m CD22 has been investigated The binding modes of Neu5Gc-/Neu5Accontaining ligands to m/h-CD22 were compared The bioactive conformation of sialoglycans has been derived Our findings may help in the regulation of immune response and cancer prevention

Nature Communications, 2014

Carbohydrate recognition is essential for growth, cell adhesion and signalling in all living orga... more Carbohydrate recognition is essential for growth, cell adhesion and signalling in all living organisms. A highly conserved carbohydrate binding module, LysM, is found in proteins from viruses, bacteria, fungi, plants and mammals. LysM modules recognize polysaccharides containing N-acetylglucosamine (GlcNAc) residues including peptidoglycan, an essential component of the bacterial cell wall. However, the molecular mechanism underpinning LysM–peptidoglycan interactions remains unclear. Here we describe the molecular basis for peptidoglycan recognition by a multimodular LysM domain from AtlA, an autolysin involved in cell division in the opportunistic bacterial pathogen Enterococcus faecalis. We explore the contribution of individual modules to the binding, identify the peptidoglycan motif recognized, determine the structures of free and bound modules and reveal the residues involved in binding. Our results suggest that peptide stems modulate LysM binding to peptidoglycan. Using these ...

Science, 2007

Endotoxic lipopolysaccharide (LPS) with potent immunostimulatory activity is recognized by the re... more Endotoxic lipopolysaccharide (LPS) with potent immunostimulatory activity is recognized by the receptor complex of MD-2 and Toll-like receptor 4. Crystal structures of human MD-2 and its complex with the antiendotoxic tetra-acylated lipid A core of LPS have been determined at 2.0 and 2.2 angstrom resolutions, respectively. MD-2 shows a deep hydrophobic cavity sandwiched by two β sheets, in which four acyl chains of the ligand are fully confined. The phosphorylated glucosamine moieties are located at the entrance to the cavity. These structures suggest that MD-2 plays a principal role in endotoxin recognition and provide a basis for antiseptic drug development.

Proceedings of the National Academy of Sciences, 2012

Lipopolysaccharide (LPS), also known as endotoxin, activates the innate immune response through t... more Lipopolysaccharide (LPS), also known as endotoxin, activates the innate immune response through toll-like receptor 4 (TLR4) and its coreceptor, MD-2. MD-2 has a unique hydrophobic cavity that directly binds to lipid A, the active center of LPS. Tetraacylated lipid IVa, a synthetic lipid A precursor, acts as a weak agonist to mouse TLR4/MD-2, but as an antagonist to human TLR4/MD-2. However, it remains unclear as to how LPS and lipid IVa show agonistic or antagonistic activities in a species-specific manner. The present study reports the crystal structures of mouse TLR4/MD-2/LPS and TLR4/MD-2/lipid IVa complexes at 2.5 and 2.7 Å resolutions, respectively. Mouse TLR4/MD-2/LPS exhibited an agonistic “m”-shaped 2:2:2 complex similar to the human TLR4/MD-2/LPS complex. Mouse TLR4/MD-2/lipid IVa complex also showed an agonistic structural feature, exhibiting architecture similar to the 2:2:2 complex. Remarkably, lipid IVa in the mouse TLR4/MD-2 complex occupied nearly the same space as LP...

ChemInform, Aug 5, 2010

Synthesis and Biological Activities of Dibenzyl Dipiperazine Diquaternary Ammonium Salts.-A serie... more Synthesis and Biological Activities of Dibenzyl Dipiperazine Diquaternary Ammonium Salts.-A series of 20 title compounds is prepared and evaluated for their analgesic, sedative, and antiinflammatory activities. (Ic) shows high antiinflammatory activity.

Comprehensive Glycoscience, 2007

The Journal of Immunology, 2008

The Journal of Immunology, 2008

Peptidoglycans (PGNs) are ubiquitous constituents of bacterial cell walls and exhibit various imm... more Peptidoglycans (PGNs) are ubiquitous constituents of bacterial cell walls and exhibit various immunobiological activities. Two types of minimum essential PGN structures for immunobiological activities were chemically synthesized and designated as muramyldipeptide; N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) and ␥-D-glutamyl-meso-diaminopimelic acid (iE-DAP), which are common constituents of both Gram-positive and Gram-negative bacteria, as well as most Gram-negative and some Grampositive bacteria, respectively. Recently, intracellular receptors for MDP and iE-DAP have been demonstrated to be nucleotidebinding oligomerization domain (NOD)1 and NOD2, respectively. In this study, we demonstrated that chemically synthesized meso-DAP itself activated human epithelial cells from various tissues, through NOD1 to generate antibacterial factors, PGN recognition proteins and ␤-defensin 2, and cytokines in specified cases, although the activities of meso-DAP were generally weaker than those of known NOD agonists. However, stereoisomers of meso-DAP, LL-DAP, and DD-DAP were only slightly activated or remained inactive, respectively. Synthetic meso-lanthionine, which is another diamino-type amino acid specific to PGN of the specified Gram-negative bacteria, was also recognized by NOD1. In human monocytic cells, in the presence of cytochalasin D meso-DAP induced slightly but significantly increased production of cytokines, although the cells did not respond to meso-DAP in the absent of cytochalasin D. Our findings suggest that NOD1 is a special sentinel molecule, especially in the epithelial barrier, allowing the intracellular detection of bacteria through recognizing meso-DAP or comparable moiety of PGN from specified bacteria in cooperation with NOD2, thereby playing a key role in innate immunity.

Tetrahedron Letters, 1991

ABSTRACT

Tetrahedron, 1995

A stereoselective glycosidation with thioglycosides was effected under mild and neutral condition... more A stereoselective glycosidation with thioglycosides was effected under mild and neutral conditions by combined use of N-bromosuccinimide (NBS) and a catalytic amount of various strong acid salts. A combination of NBS with Ph2IOTf, Bu4NOTf, or Bu4NClO4 was advantageous for β-selective glucosidation with 2-O-acylated or 2-O-benzylated donors by virtue of either the neighboring group participation or the known solvent effect of

Bulletin of the Chemical Society of Japan, 1985

ABSTRACT

Biopolymers, 1989

We report progress in elucidating the structure of nisin, a naturally occurring peptide antibioti... more We report progress in elucidating the structure of nisin, a naturally occurring peptide antibiotic. Ninin contains five rings constrained by lanthionine or methyllanthionine bridges, as well as a,/3-unsaturated amino acids. We have determined conformations for two model compounds of ring A and a derivative of ring B through interactive nmr and computer simulation studies. High-resolution nmr techniques provides structural information, which was further refined through molecular dynamics simulations. These methods are being applied to the remeing constrained fragments of the molecule. This conformational information w i l l be employed in an aufbau approach to determining the structure of the entire molecule. compounds. In this manner we have determined conformations for con-*To whom correspondence should be addressed.

Nod1 is an intracellular protein that is involved in recognition of bacterial molecules and whose... more Nod1 is an intracellular protein that is involved in recognition of bacterial molecules and whose genetic variation has been linked to several inflammatory diseases. Previous studies suggested that the recognition core of Nod1stimulatory molecules is γ-D-glutamyl-mesodiaminopimelic acid (iE-DAP), but the identity of the major Nod1-stimulatory molecule produced by bacteria remains unknown. Here we show that bacteria produce lipophilic molecules capable of stimulating Nod1. Analysis of synthetic compounds revealed stereoselectivity of the DAP residue and that conjugation of lipophilic acyl residues specifically enhances the Nod1-stimulatory activity of the core iE-DAP. Furthermore, we demonstrate that lipophilic molecules induce and/or enhance the secretion of innate immune mediators from primary mouse mesothelial cells and human monocytic MonoMac6 cells and this effect is mediated through Nod1. These results provide insight into the mechanism of immune recognition via Nod1 which might be useful in design and testing of novel immunoregulators. The innate immune receptors recognize specific molecules that are commonly found in microbes and induce host defense responses to eliminate invading pathogens (1). These pathogen-recognizing receptors (PRRs) include membrane-bound Toll-like receptors (TLRs) as well as cytosolic Nod-like receptors (NLRs) and RIG-I family proteins. These three classes of

Bulletin of the Chemical Society of Japan, 1991

ChemInform, 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Journal of Clinical Investigation, 2000

iScience

The structural basis of sialoglycans recognition by h/m CD22 has been investigated The binding mo... more The structural basis of sialoglycans recognition by h/m CD22 has been investigated The binding modes of Neu5Gc-/Neu5Accontaining ligands to m/h-CD22 were compared The bioactive conformation of sialoglycans has been derived Our findings may help in the regulation of immune response and cancer prevention

Nature Communications, 2014

Carbohydrate recognition is essential for growth, cell adhesion and signalling in all living orga... more Carbohydrate recognition is essential for growth, cell adhesion and signalling in all living organisms. A highly conserved carbohydrate binding module, LysM, is found in proteins from viruses, bacteria, fungi, plants and mammals. LysM modules recognize polysaccharides containing N-acetylglucosamine (GlcNAc) residues including peptidoglycan, an essential component of the bacterial cell wall. However, the molecular mechanism underpinning LysM–peptidoglycan interactions remains unclear. Here we describe the molecular basis for peptidoglycan recognition by a multimodular LysM domain from AtlA, an autolysin involved in cell division in the opportunistic bacterial pathogen Enterococcus faecalis. We explore the contribution of individual modules to the binding, identify the peptidoglycan motif recognized, determine the structures of free and bound modules and reveal the residues involved in binding. Our results suggest that peptide stems modulate LysM binding to peptidoglycan. Using these ...

Science, 2007

Endotoxic lipopolysaccharide (LPS) with potent immunostimulatory activity is recognized by the re... more Endotoxic lipopolysaccharide (LPS) with potent immunostimulatory activity is recognized by the receptor complex of MD-2 and Toll-like receptor 4. Crystal structures of human MD-2 and its complex with the antiendotoxic tetra-acylated lipid A core of LPS have been determined at 2.0 and 2.2 angstrom resolutions, respectively. MD-2 shows a deep hydrophobic cavity sandwiched by two β sheets, in which four acyl chains of the ligand are fully confined. The phosphorylated glucosamine moieties are located at the entrance to the cavity. These structures suggest that MD-2 plays a principal role in endotoxin recognition and provide a basis for antiseptic drug development.

Proceedings of the National Academy of Sciences, 2012

Lipopolysaccharide (LPS), also known as endotoxin, activates the innate immune response through t... more Lipopolysaccharide (LPS), also known as endotoxin, activates the innate immune response through toll-like receptor 4 (TLR4) and its coreceptor, MD-2. MD-2 has a unique hydrophobic cavity that directly binds to lipid A, the active center of LPS. Tetraacylated lipid IVa, a synthetic lipid A precursor, acts as a weak agonist to mouse TLR4/MD-2, but as an antagonist to human TLR4/MD-2. However, it remains unclear as to how LPS and lipid IVa show agonistic or antagonistic activities in a species-specific manner. The present study reports the crystal structures of mouse TLR4/MD-2/LPS and TLR4/MD-2/lipid IVa complexes at 2.5 and 2.7 Å resolutions, respectively. Mouse TLR4/MD-2/LPS exhibited an agonistic “m”-shaped 2:2:2 complex similar to the human TLR4/MD-2/LPS complex. Mouse TLR4/MD-2/lipid IVa complex also showed an agonistic structural feature, exhibiting architecture similar to the 2:2:2 complex. Remarkably, lipid IVa in the mouse TLR4/MD-2 complex occupied nearly the same space as LP...

ChemInform, Aug 5, 2010

Synthesis and Biological Activities of Dibenzyl Dipiperazine Diquaternary Ammonium Salts.-A serie... more Synthesis and Biological Activities of Dibenzyl Dipiperazine Diquaternary Ammonium Salts.-A series of 20 title compounds is prepared and evaluated for their analgesic, sedative, and antiinflammatory activities. (Ic) shows high antiinflammatory activity.

Comprehensive Glycoscience, 2007

The Journal of Immunology, 2008

The Journal of Immunology, 2008

Peptidoglycans (PGNs) are ubiquitous constituents of bacterial cell walls and exhibit various imm... more Peptidoglycans (PGNs) are ubiquitous constituents of bacterial cell walls and exhibit various immunobiological activities. Two types of minimum essential PGN structures for immunobiological activities were chemically synthesized and designated as muramyldipeptide; N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) and ␥-D-glutamyl-meso-diaminopimelic acid (iE-DAP), which are common constituents of both Gram-positive and Gram-negative bacteria, as well as most Gram-negative and some Grampositive bacteria, respectively. Recently, intracellular receptors for MDP and iE-DAP have been demonstrated to be nucleotidebinding oligomerization domain (NOD)1 and NOD2, respectively. In this study, we demonstrated that chemically synthesized meso-DAP itself activated human epithelial cells from various tissues, through NOD1 to generate antibacterial factors, PGN recognition proteins and ␤-defensin 2, and cytokines in specified cases, although the activities of meso-DAP were generally weaker than those of known NOD agonists. However, stereoisomers of meso-DAP, LL-DAP, and DD-DAP were only slightly activated or remained inactive, respectively. Synthetic meso-lanthionine, which is another diamino-type amino acid specific to PGN of the specified Gram-negative bacteria, was also recognized by NOD1. In human monocytic cells, in the presence of cytochalasin D meso-DAP induced slightly but significantly increased production of cytokines, although the cells did not respond to meso-DAP in the absent of cytochalasin D. Our findings suggest that NOD1 is a special sentinel molecule, especially in the epithelial barrier, allowing the intracellular detection of bacteria through recognizing meso-DAP or comparable moiety of PGN from specified bacteria in cooperation with NOD2, thereby playing a key role in innate immunity.

Tetrahedron Letters, 1991

ABSTRACT

Tetrahedron, 1995

A stereoselective glycosidation with thioglycosides was effected under mild and neutral condition... more A stereoselective glycosidation with thioglycosides was effected under mild and neutral conditions by combined use of N-bromosuccinimide (NBS) and a catalytic amount of various strong acid salts. A combination of NBS with Ph2IOTf, Bu4NOTf, or Bu4NClO4 was advantageous for β-selective glucosidation with 2-O-acylated or 2-O-benzylated donors by virtue of either the neighboring group participation or the known solvent effect of

Bulletin of the Chemical Society of Japan, 1985

ABSTRACT

Biopolymers, 1989

We report progress in elucidating the structure of nisin, a naturally occurring peptide antibioti... more We report progress in elucidating the structure of nisin, a naturally occurring peptide antibiotic. Ninin contains five rings constrained by lanthionine or methyllanthionine bridges, as well as a,/3-unsaturated amino acids. We have determined conformations for two model compounds of ring A and a derivative of ring B through interactive nmr and computer simulation studies. High-resolution nmr techniques provides structural information, which was further refined through molecular dynamics simulations. These methods are being applied to the remeing constrained fragments of the molecule. This conformational information w i l l be employed in an aufbau approach to determining the structure of the entire molecule. compounds. In this manner we have determined conformations for con-*To whom correspondence should be addressed.

Nod1 is an intracellular protein that is involved in recognition of bacterial molecules and whose... more Nod1 is an intracellular protein that is involved in recognition of bacterial molecules and whose genetic variation has been linked to several inflammatory diseases. Previous studies suggested that the recognition core of Nod1stimulatory molecules is γ-D-glutamyl-mesodiaminopimelic acid (iE-DAP), but the identity of the major Nod1-stimulatory molecule produced by bacteria remains unknown. Here we show that bacteria produce lipophilic molecules capable of stimulating Nod1. Analysis of synthetic compounds revealed stereoselectivity of the DAP residue and that conjugation of lipophilic acyl residues specifically enhances the Nod1-stimulatory activity of the core iE-DAP. Furthermore, we demonstrate that lipophilic molecules induce and/or enhance the secretion of innate immune mediators from primary mouse mesothelial cells and human monocytic MonoMac6 cells and this effect is mediated through Nod1. These results provide insight into the mechanism of immune recognition via Nod1 which might be useful in design and testing of novel immunoregulators. The innate immune receptors recognize specific molecules that are commonly found in microbes and induce host defense responses to eliminate invading pathogens (1). These pathogen-recognizing receptors (PRRs) include membrane-bound Toll-like receptors (TLRs) as well as cytosolic Nod-like receptors (NLRs) and RIG-I family proteins. These three classes of

Bulletin of the Chemical Society of Japan, 1991