Carbohydrate Binding Specificity of the Recombinant Chitin-binding Domain of Human Macrophage Chitinase

Ujita, Minoru; Sakai, Kaori; Hamazaki, Keishi; Yoneda, Masahiko; Isomura, Shigeki; Hara, Akira

doi:10.1271/bbb.67.2402

Cited by 20 publications

(13 citation statements)

References 15 publications

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“…This N-terminal CBD, which is also present in the Jessie lectin (Figure 3(b)), contains 8 conserved cysteine (Cys) residues that form four disulfide bonds, as well as numerous conserved aromatic amino acids that likely bind the sugar rings of chitin [10,14,16]. Yeast and human chitinases have C-terminal CBDs that do not share common ancestry with that of Entamoeba [17,18]. …”

Section: Cyst Wall Chitinase and Jessie Lectins Have A Single Uniquementioning

confidence: 99%

A simple fibril and lectin model for cyst walls of Entamoeba and perhaps Giardia

Samuelson

Robbins

2011

Trends in Parasitology

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Cyst walls of Entamoeba and Giardia protect them from environmental insults, stomach acids, and intestinal proteases. Each cyst wall contains a sugar homopolymer: chitin in Entamoeba and a unique N-acetylgalactosamine (GalNAc) homopolymer in Giardia. Entamoeba cyst wall proteins include Jacob lectins (carbohydrate-binding proteins) that cross-link chitin, chitinases that degrade chitin, and Jessie lectins that make walls impermeable. Giardia cyst wall proteins are also lectins that bind fibrils of the GalNAc homopolymer. While many of the details remain to be determined for the Giardia cyst wall, current data suggests a relatively simple fibril and lectin model for the Entamoeba cyst wall. Why cyst walls are importantEntamoeba histolytica, the cause of amebic dysentery and liver abscess, and Giardia lamblia, a cause of diarrhea, are both spread by the fecal-oral route (Figure 1). Tetranucleate cysts of Entamoeba and Giardia are the diagnostic and infectious stage of each parasite [1,2]. The cyst wall, which is hard and impermeable to small molecules, protects Entamoeba and Giardia from lysis by environmental insults such as osmotic shock in fresh water, stomach acid, and duodenal proteases. Conversely, the cyst wall is quickly broken when parasites excyst and colonize the epithelium of the colon (Entamoeba) and duodenum (Giardia).Major issues for each organism are the composition of the cyst wall, how it is constructed, and how it is broken when the parasites excyst. Other important issues that will not be extensively discussed are the stimuli that trigger encystation and excystation, signals that mediate these stimuli, Golgi apparatus function, and the mechanisms whereby encysting protists secrete vast amounts of proteins and carbohydrates onto their surfaces [3][4][5][6]. Recent progress has been made on understanding how the Entamoeba cyst wall becomes impermeable to small molecules and how cyst wall proteins of Giardia bind to fibrils of the GalNAc homopolymer.

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Section: Cyst Wall Chitinase and Jessie Lectins Have A Single Uniquementioning

confidence: 99%

A simple fibril and lectin model for cyst walls of Entamoeba and perhaps Giardia

Samuelson

Robbins

2011

Trends in Parasitology

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“…The An15g07370 gene was found among the ten genes with the highest level of transcription in the aerial structures . CBM14 members are capable of binding chitin in the fungal cell walls (Tjoelker et al, 2000;Ujita et al, 2003) and may either protect the chitin polymer from degradation (van den Burg et al, 2006) or assist the activity of chitinolytic enzymes. In contrast to chitin synthase chsC, the genes encoding the protein harbouring the CBM14 and the chitinolytic enzymes were expressed only at relatively low levels in dormant conidia and were absent in germinating conidia.…”

Section: Chitin Modification In Aerial Structuresmentioning

confidence: 99%

Chitinases CtcB and CfcI modify the cell wall in sporulating aerial mycelium of Aspergillus niger

et al. 2013

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Sporulation is an essential part of the life cycle of the industrially important filamentous fungus Aspergillus niger. The formation of conidiophores, spore-bearing structures, requires remodelling of the fungal cell wall, as demonstrated by the differences in carbohydrate composition of cell walls of vegetative mycelium and spores. Glycoside hydrolases that are involved in this process have so far remained unidentified. Using transcriptome analysis, we have identified genes encoding putative cell-wall-modifying proteins with enhanced expression in sporulating aerial mycelium compared to vegetative mycelium. Among the most strongly induced genes were those encoding a protein consisting of a putative chitin binding module (CBM14) and the chitinolytic enzymes NagA, CfcI and CtcB. Reporter studies showed that the N-acetyl-b-hexosaminidase gene nagA was expressed both in vegetative hyphae and in aerial structures (aerial hyphae, conidiophores and conidia) upon starvation. In contrast, promoter activities of the chitinase genes ctcB and cfcI were specifically localized in the conidiophores and conidia. CtcB is an endochitinase and CfcI releases monomers from chitin oligosaccharides: together these enzymes have the potential to degrade chitin of the fungal cell wall. Inactivation of both the cfcI and ctcB genes affected neither radial growth rate, nor formation and germination of spores. The amount of chitin in the spore walls of a DcfcIDctcB double deletion strain, however, was significantly increased compared with the wild-type, thus indicating that CfcI and CtcB indeed modify the A. niger cell walls during sporulation. These novel insights in the sporulation process in aspergilli are of strong scientific relevance, and also may aid industrial strain engineering.

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“…The presence or increased appearance of β1-6 GlcNAc branching occurs in carcinogenesis in many cancers (2). Several in-vivo studies have shown that the expression of GnT-V and the presence of β1-6 GlcNAc branching play a functional role in carcinogenesis and are associated with metastasis and poor prognosis at least in cancers of the breast (3–9) and colon-rectum (3) and melanoma (4). Studies involving attempts to inhibit the formation of β1-6 branching have shown therapeutic effects in murine and human cancer cells (5, 6).…”

Section: Glycans Chitins and Carcinogenesismentioning

confidence: 99%

“…Although no mammalian chitin synthases have been reported, chitinases are produced by mammalian macrophages in what is thought to be a defense mechanism against chitin-containing pathogens (9). In an intriguing 2005 study, administration of bacterial chitinases produced breast-cancer regression in vitro and in vivo; human tumor cells were selectively lysed by chitinase in culture and in mouse xenografts (10).…”

Section: Glycans Chitins and Carcinogenesismentioning

confidence: 99%

Chitin or Chitin-Like Glycans as Targets for Late-Term Cancer Chemoprevention

Wattenberg

Patterson

Antonides

2010

Cancer Prevention Research

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A consistent observation in studies of carcinogenesis is that some glycans are expressed differently in cancer cells than in normal cells. A well-known example is the aberrant b1-6 N-acetyl-D-glucosamine branching associated with metastasis and poor prognosis in many cancers. This commentary proposes that, although not found in normal mammalian cells, a chitin (b-1,4-linked N-acetyl-D-glucosamine) or a chitin-like polysaccharide (e.g., hyaluronan) may exist as a cancer-associated glycan, which can be targeted by the novel pyrimidine nucleotide derivative SP-1015 (designed as a chitin synthase inhibitor). Preliminary chemoprevention data of our group showed SP-1015 in the diet can inhibit benzo(a)pyreneinduced neoplasia in the forestomach of female A/J mice, and, of importance, this activity occurred at late stages in carcinogenesis. While no effect was seen in the murine lung, this may be due to the low bioavailability of the compound. A different route of administration (e.g. inhalation of an aerosol) may have potential to inhibit pulmonary carcinogenesis. We hypothesize that inhibitors of chitin or chitin-like glycan formation may be effective chemopreventive agents and suggest that further work is needed to study these novel targets for cancer prevention. Cancer Prev Res; 3(12); 1519-22. Ó2010 AACR. Glycans, Chitins, and CarcinogenesisA consistent observation in studies of carcinogenesis is that expression of glycans is different in cancer cells than in normal cells. Glycans-oligosaccharides or polysaccharides often attached to proteins or lipids-are found on the surfaces of all eukaryotic cells and in the extracellular matrix and some organelles. Glycans are formed in the process of glycosylation through the creation of glycosidic linkages, the bonds between carbohydrate units and other molecules. During glycosylation in the Golgi apparatus, glycotransferases (enzymes which form glycosidic linkages) and glycosidases (enzymes which cleave glycosidic linkages) often exhibit changed levels of expression in cancer cells compared with their normal cell counterparts. The resulting aberrant glycosylation leads to changes in the core glycan structure, such as altered branching and increased glycan size, and can lead to other changes in chemical composition associated with carcinogenesis. Thus, over-or underexpression of particular glycans, generally structurally modified from their normal-cell counterparts, is characteristic of cancer cells (reviewed in refs. 1-5).Perhaps the most-widely studied example of an aberrant structure associated with cancer cell surfaces is the occurrence of b1-6 branching on N-glycans between N-acetyl-D-glucosamine (GlcNAc) and mannose (Man). This branching is caused by the activity of the glycotransferase N-acetlyglucosaminyltransferase-V (GnT-V), which catalyzes the addition of GlcNAc to a particular Man residue on an asparagine-linked glycan, forming the branching structure GlcNAcb1-6-Mana1-6Manb1 ( Fig. 1; refs. 1-5). The additional branch provides an additional substrate for ...

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Carbohydrate Binding Specificity of the Recombinant Chitin-binding Domain of Human Macrophage Chitinase

Cited by 20 publications

References 15 publications

A simple fibril and lectin model for cyst walls of Entamoeba and perhaps Giardia

A simple fibril and lectin model for cyst walls of Entamoeba and perhaps Giardia

Chitinases CtcB and CfcI modify the cell wall in sporulating aerial mycelium of Aspergillus niger

Chitin or Chitin-Like Glycans as Targets for Late-Term Cancer Chemoprevention

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