Lectins from the Edible Mushroom Agaricus bisporus and Their Therapeutic Potentials

Abstract

The mushroom Agaricus bisporus secretes biologically active compounds and proteins with benefits for human health. Most reported proteins from A. bisporus are tyrosinases and lectins. Lectins are of therapeutic or pharmaceutical interest. To date, only limited information is available on A. bisporus lectins and lectin-like proteins. No therapeutic products derived from A. bisporus lectin (ABL) are available on the market despite its extensive exploration. Recently, A. bisporus mannose-binding protein (Abmb) was discovered. Its discovery enriches the information and increases the interest in proteins with therapeutic potential from this mushroom. Furthermore, the A. bisporus genome reveals the possible occurrence of other lectins in this mushroom that may also have therapeutic potential. Most of these putative lectins belong to the same lectin groups as ABL and Abmb. Their relationship is discussed. Particular attention is addressed to ABL and Abmb, which have been explored for their potential in medicinal or pharmaceutical applications. ABL and Abmb have anti-proliferative activities toward cancer cells and a stimulatory effect on the immune system. Possible scenarios for their use in therapy and modification are also presented.

Keywords: anticancer; biological active fraction; immunomodulator; sugar-binding proteins; therapeutic protein.

Figure 1

Alignment of amino acid sequences of A. bisporus lectin (ABL) (XP_006455249) and two of its closest putative lectin homologs in the A. bisporus U97 genomic library [27]. The protein annotations are according to the GenBank ID; the asterisk (*), colon (:), and period (.) signs indicate the identical, conserved, and similar amino acid residues, respectively.

Figure 2

Alignment of amino acid sequences of the homologous putative Ricin B-like lectins [27]. The (Gln-x-Trp)₃ canonical sequence motifs of β-trefoil fold are highlighted in boxes. The protein annotations are according to the GenBank ID; the asterisk (*), colon (:), and period (.) signs indicate the identical, conserved, and similar amino acid residues, respectively.

Figure 3

A phylogenetic relationship between fungal and plant lectins as presented by van Holle and van Damme [28].

Figure 4

(a) Secondary structure topology of ABL. The pleated forms indicate the arrangement of the β-strands assembly. (b) Cartoon presentation of the crystal structure of ABL (Protein Data Bank (PDB) ID: 1Y2T). The structure was obtained from the Protein Databank and the three-dimensional structure figure was prepared using PyMoL [44]. The secondary structure topology was manually prepared using the three-dimensional structure as the reference.

Figure 5

(a) The gene assembly in the region surrounding the Abmb encoding gene [4]. Numbers on the right refer to the position of the gene in the nucleotide genome sequence. AT stands for (4-hydroxy)phenylpyruvate amino transferase (b) Phylogenetic relationship between Abmb (GenBank ID XM_006459649) with other putative Ricin B-like lectins in A. bisporus. The phylogenetic tree was generated upon the amino acid sequence alignment using the program ClustalOmega [27]. PPO, polyphenol oxidase; Abmb, A. bisporus mannose-binding protein.

Figure 6

Cartoon presentation of the crystal structure of (a) Abmb (PDB ID: 5EHA) and (b) the tetrameric complex of PPO3–Abmb (PDB ID 2 × 9Y). In the PPO3–Abmb complex, the tyrosinase is at the bottom, while the Abmb molecules are at the top. The structure was obtained from the Protein Databank. The three-dimensional structure figure was prepared using PyMoL [44].

Figure 7

Illustration of an Abmb bioconjugate carrying an anticancer drug upon recognition by a receptor (presumably a sugar) on the cell surface.