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Crystal Structure of Agrocybe aegerita lectin AAL mutant R85A complexed with p-Nitrophenyl TF disaccharide
Structural highlights
FunctionATLE_CYCAE Anti-tumor lectin with DNase activity. Inhibits the growth of several tumor cell lines in vitro. Induces lymphocyte infiltration and necrosis of tumor cells in a mouse tumor model. Induces apoptosis in HeLa cells. Binds N-acetylneuraminyl lactose (N-acetyl-alpha-neuraminyl-(2->3)-beta-D-galactosyl-(1->4)-beta-D-glucose) (PubMed:16051274).[1] [2] Publication Abstract from PubMedThomsen-Friedenreich (TF) antigen, which plays an important role in the regulation of cancer cell proliferation, occurs in approximately 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. Structural insights into the recognition mechanism between an antitumor galectin AAL and the Thomsen-Friedenreich antigen.,Feng L, Sun H, Zhang Y, Li DF, Wang DC FASEB J. 2010 Oct;24(10):3861-8. Epub 2010 Jun 7. PMID:20530247[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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