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PDBsum entry 1y2t
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Sugar binding protein
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PDB id
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1y2t
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References listed in PDB file
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Key reference
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Title
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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.
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Authors
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M.E.Carrizo,
S.Capaldi,
M.Perduca,
F.J.Irazoqui,
G.A.Nores,
H.L.Monaco.
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Ref.
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J Biol Chem, 2005,
280,
10614-10623.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 4.
FIG. 4. The two binding sites in a monomer. Stereodiagram
of a monomer of ABL with a molecule of N-acetylgalactosamine
(NGA) bound at the T-antigen binding site (top) and a molecule
of N-acetylglucosamine (NAG) bound at the second binding site
(bottom). The electron density of the 2Fobs-Fc map corresponds
to the ligands bound in the orthorhombic form, and it was
contoured at the 1.5  level. The side chains
of the main amino acids involved in the interactions are
represented in the figure. The figure was prepared using the
program DINO (www.dino3d.org).
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Figure 5.
FIG. 5. Sequence comparison of fungal lectins. The
sequences were aligned using the program CLUSTALW (43) and
correspond to the following lectins: XCL, X. chrysenteron
lectin; PCL, P. cornucopiae lectin; AOL, A. oligospora lectin;
PAL, P. anserina lectin; and NCL, N. crassa lectin. The residues
involved in the binding of the T antigen to ABL are indicated
with a T, and those that participate in the binding of
N-acetylglucosamine are indicated with an N. The residues
conserved in all the members of the group are represented in red.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2005,
280,
10614-10623)
copyright 2005.
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Secondary reference #1
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Title
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Crystallization and preliminary X-Ray study of the common edible mushroom (agaricus bisporus) lectin.
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Authors
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M.E.Carrizo,
F.J.Irazoqui,
R.D.Lardone,
G.A.Nores,
J.A.Curtino,
S.Capaldi,
M.Perduca,
H.L.Monaco.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2004,
60,
718-720.
[DOI no: ]
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PubMed id
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Figure 1.
Figure 1 (a) Analytical isoelectric focusing showing ABL. Left
lane, after the affinity chromatography step: the five isoforms
are visible. Right lane, after the preparative isolectric
focusing step: this separated the most basic form, which was
crystallized. (b) Crystals of ABL grown by the hanging-drop
method. The size of the largest crystal is approximately 0.3 ×
0.3 × 0.1 mm.
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The above figure is
reproduced from the cited reference
with permission from the IUCr
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