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Structural insights into the recognition mechanism between an antitumor galectin AAL and the Thomsen-Friedenreich antigen.


ABSTRACT: Thomsen-Friedenreich (TF) antigen, which plays an important role in the regulation of cancer cell proliferation, occurs in ?90% of all human cancers and precancerous conditions. Although TF antigen has been known for almost 80 yr as a pancarcinoma antigen, the recognition mechanism between TF antigen and target protein has not been structurally characterized. A number of studies indicated that TF disaccharide is a potential ligand of the galactoside-binding galectins. In this work, we identified the TF antigen as a potential ligand of the antitumor galectin AAL (Agrocybe aegerita lectin) through glycan array analysis and reported the crystal structure of AAL complexed with the TF antigen. The structure provides a first look at the recognition mode between AAL and TF antigen, which is unique in a conservative (Glu-water-Arg-water) structural motif-based hydrogen bond network. Structure-based mutagenesis analysis further revealed the residues responsible for recognition specificity and binding affinity. Crystal structures of AAL complexed with two other TF-containing glycans showed that the unique TF recognition mode is kept intact, which may be commonly adopted in some cancer-related galectins. The finding provided the new target and approach for the antitumor drug design and relative strategy based on the AAL-TF recognition mode as a prototype model.

SUBMITTER: Feng L 

PROVIDER: S-EPMC3229422 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Structural insights into the recognition mechanism between an antitumor galectin AAL and the Thomsen-Friedenreich antigen.

Feng Lei L   Sun Hui H   Zhang Ying Y   Li De-Feng DF   Wang Da-Cheng DC  

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20100607 10


Thomsen-Friedenreich (TF) antigen, which plays an important role in the regulation of cancer cell proliferation, occurs in ∼90% of all human cancers and precancerous conditions. Although TF antigen has been known for almost 80 yr as a pancarcinoma antigen, the recognition mechanism between TF antigen and target protein has not been structurally characterized. A number of studies indicated that TF disaccharide is a potential ligand of the galactoside-binding galectins. In this work, we identified  ...[more]

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