| Structural highlights
Function
[ABL_AGABI] Lectin that recognizes O-linked galactose-beta-1,3-N-acetylgalactosamine, a disaccharide (Thomsen-Friedenreich antigen or T-disaccharide), present on cell surface glycoproteins. Can also bind galactose-beta-1,3-N-acetylglucosamine. Does not bind monosaccharides. Can be internalized by clathrin-coated vesicles after binding to surface glycoproteins. After internalization it inhibits nuclear import of nuclear localization signal dependent proteins. Inhibits proliferation of malignant cells without cytotoxicity for normal cells.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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 beta 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, Galbeta1-3GalNAc, 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, N-acetylglucosamine, 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.
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.,Carrizo ME, Capaldi S, Perduca M, Irazoqui FJ, Nores GA, Monaco HL J Biol Chem. 2005 Mar 18;280(11):10614-23. Epub 2004 Dec 13. PMID:15596442[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Presant CA, Kornfeld S. Characterization of the cell surface receptor for the Agaricus bisporus hemagglutinin. J Biol Chem. 1972 Nov 10;247(21):6937-45. PMID:4343164
- ↑ Yu L, Fernig DG, Smith JA, Milton JD, Rhodes JM. Reversible inhibition of proliferation of epithelial cell lines by Agaricus bisporus (edible mushroom) lectin. Cancer Res. 1993 Oct 1;53(19):4627-32. PMID:8402638
- ↑ Yu LG, Fernig DG, White MR, Spiller DG, Appleton P, Evans RC, Grierson I, Smith JA, Davies H, Gerasimenko OV, Petersen OH, Milton JD, Rhodes JM. Edible mushroom (Agaricus bisporus) lectin, which reversibly inhibits epithelial cell proliferation, blocks nuclear localization sequence-dependent nuclear protein import. J Biol Chem. 1999 Feb 19;274(8):4890-9. PMID:9988731
- ↑ Carrizo ME, Capaldi S, Perduca M, Irazoqui FJ, Nores GA, Monaco HL. 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. J Biol Chem. 2005 Mar 18;280(11):10614-23. Epub 2004 Dec 13. PMID:15596442 doi:10.1074/jbc.M411989200
|
