The Antineoplastic Lectin of the Common Edible Mushroom (Agaricus bisporus) Has Two Binding Sites, Each Specific for a Different Configuration at a Single Epimeric Hydroxyl

Abstract

The lectin from the common mushroom Agaricus bisporus, the most popular edible species in Western countries, has potent antiproliferative effects on human epithelial cancer cells, without any apparent cytotoxicity. This property confers to it an important therapeutic potential as an antineoplastic agent. The three-dimensional structure of the lectin was determined by x-ray diffraction. The protein is a tetramer with 222 symmetry, and each monomer presents a novel fold with two ␤ sheets connected by a helix-loop-helix motif. Selectivity was studied by examining the binding of four monosaccharides and seven disaccharides in two different crystal forms. The T-antigen disaccharide, Gal␤1-3GalNAc, mediator of the antiproliferative effects of the protein, binds at a shallow depression on the surface of the molecule. The binding of N-acetylgalactosamine overlaps with that moiety of the T antigen, but surprisingly, Nacetylglucosamine, which differs from N-acetylgalactosamine only in the configuration of epimeric hydroxyl 4, binds at a totally different site on the opposite side of the helix-loop-helix motif. The lectin thus has two distinct binding sites per monomer that recognize the different configuration of a single epimeric hydroxyl. The structure of the protein and its two carbohydrate-binding sites are described in detail in this study.

Entomotoxic and nematotoxic lectins and protease inhibitors from fungal fruiting bodies

“…It was suggested that the archetypal actinoporin fold is used for specific binding to various molecules at the plasma membrane surface (Kristan et al 2009). Characterized representatives of the actinoporin-type mushroom lectin family include XCL, ABL (ABA), SRL, and BEL from the basidiomycetes Xerocomus (Boletus) chrysenteron, Agaricus bisporus, Sclerotium (Athelia) rolfsii, and B. edulis (Birck et al 2004;Bovi et al 2011;Carrizo et al 2005;Leonidas et al 2007) and AOL 2 and TAP1 from the ascomycetes Arthrobotrys oligospora and Sordaria macrospora (Nowrousian and Cebula 2005;Rosen et al 1996b). These representatives of basidiomycetes share 53 to 82 % sequence identity (67 to 89 % similarity), while AOL 2 is approximately 45 % identical (62 % similar) to them and TAP1 only 34 % identical (50 % similar).…”

“…1). SRL was shown to be a dimer but can, from a structural point of view, form similar tetramers as other representatives (Birck et al 2004;Bovi et al 2011;Carrizo et al 2005;Leonidas et al 2007).…”

Structural and Thermodynamic Analyses of Solute-binding Protein from Bifidobacterium longum Specific for Core 1 Disaccharide and Lacto-N-biose I

“…Some lectins recognize exposed T-antigen glycosides only (e.g. peanut agglutinin and ABL) (59,68); however, some lectins can recognize cryptic T-antigens masked by modifying sugar units such as sialic acids. The binding specificity of GL-BP is higher compared with lectins; it recognizes only the exposed nonreducing GNB or LNB portion without any modifications, and the affinity is stronger compared with lectins.…”

“…The parameters of LNB and T-antigen (Gal␤1-3GalNAc-␣-O-Ser) bound to the Agaricus bisporus lectin (ABL) (59) are shown in the Table 3. The conformation of LNT bound to GL-BP is similar to that of LNT in solution.…”

“…Comparison with Lectins and Potential Value of GL-BP for Diagnostic Application-To the best of our knowledge, GL-BP is the first example of an SBP having a strong affinity to LNB and GNB; however, a number of lectin structures complexed with these disaccharides have been reported (59,(62)(63)(64)(65)(66)(67). A common feature of the binding site of lectins for GNB or Tantigens is a shallow depression on the surface of the protein, and recognition occurs through hydrogen bonds to hydroxyls and stacking interaction to one side of the sugar.…”