Crystal structure and ligand selectivity of the antineoplastic lectin from the common edible mushroom (Agaricus bisporus)

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 threedimensional 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 beta sheets connected by a helix-loop-helix motif. Selectivity was studied by examining the binding of four monosacharides and seven disaccharides in two different crystal forms. The T-antigen disaccharide, Galβ1- 3GalNAc, 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, N-acetylglucosamine binds at a totally different site on the opposite side of the helix-loophelix motif. The lectin has thus two distinct binding sites per monomer that recognize the different configuration of a single epimeric hydroxyl.