INVESTIGADORES
IRAZOQUI Fernando Jose
artículos
Título:
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.
Autor/es:
CARRIZO ME,; CAPALDI S,; PERDUCA M,; FERNANDO JOSE IRAZOQUI; NORES GA,; MONACO H.,
Revista:
JOURNAL OF BIOLOGICAL CHEMISTRY
Referencias:
Año: 2005 vol. 280 p. 10614 - 10623
ISSN:
0021-9258
Resumen:
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*
THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 280, No. 11, Issue of March 18, pp. 1061410623, 2005
© 2005 by The American Society for Biochemistry and Molecular Biology, Inc. Printed in U.S.A.
Maria E. Carrizo§, Stefano Capaldi, Massimiliano Perduca, Fernando J. Irazoqui¶,
Gustavo A. Nores¶, and Hugo L. Monaco_
From the Biocrystallography Laboratory, Department of Science and Technology, University of Verona,
Strada Le Grazie 15, 37134 Verona, Italy and ¶Department of Biological Chemistry, Faculty of Chemical Sciences,
National University of Co´rdoba, Ciudad Universitaria, 5000 Co´rdoba, Argentina
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_13GalNAc,
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.