3AFK

Crystal Structure of Agrocybe aegerita lectin AAL complexed with Thomsen-Friedenreich antigen

Summary for 3AFK

• Entry DOI: 10.2210/pdb3afk/pdb
• Related: 3M3C 3M3E 3M3O 3M3Q
• Related PRD ID: PRD_900084
• Descriptor: Anti-tumor lectin, beta-D-galactopyranose-(1-3)-2-acetamido-2-deoxy-alpha-D-galactopyranose, THREONINE, ... (4 entities in total)
• Functional Keywords: galectin, aal, thomsen-friedenreich antigen, apoptosis, hydrolase, lectin, nuclease, gal-beta-1, 3-galnac-alpha-o-thr
• Biological source: Agrocybe aegerita (Black poplar mushroom)
• Total number of polymer chains: 2
• Total formula weight: 37365.24

Authors

Feng, L.,Li, D.,Wang, D. (deposition date: 2010-03-09, release date: 2010-12-01, Last modification date: 2024-03-13)

Primary citation

Feng, L.,Sun, H.,Zhang, Y.,Li, D.F.,Wang, D.C.
Structural insights into the recognition mechanism between an antitumor galectin AAL and the Thomsen-Friedenreich antigen
Faseb J., 24:3861-3868, 2010

PubMed 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.

PubMed: 20530247
DOI: 10.1096/fj.10-159111

Experimental method

X-RAY DIFFRACTION (1.95 Å)