In silico analysis of molecular mechanisms of Galanthus nivalis agglutinin-related lectin-induced cancer cell death from carbohydrate-binding motif evolution hypothesis.

Abstract

Galanthus nivalis agglutinin-related lectins, a superfamily of strictly mannose-binding-specific lectins widespread amongst monotyledonous plants, have drawn a rising attention for their remarkable anti-proliferative and apoptosis-inducing activities toward various types of cancer cells; however, the precise molecular mechanisms by which they induce tumor cell apoptosis are still only rudimentarily understood. Herein, we found that the three conserved motifs "QXDXNXVXY," the mannose-specific binding sites, could mutate at one or more amino acid sites, which might be a driving force for the sequential evolution and thus ultimately leading to the complete disappearance of the three conserved motifs. In addition, we found that the motif evolution could result in the diversification of sugar-binding types that G. nivalis agglutinin-related lectins could bind from specific mannose receptors to more types of sugar-containing receptors in cancer cells. Subsequently, we indicated that some sugar-containing receptors such as TNFR1, EGFR, Hsp90, and Hsp70 could block downstream anti-apoptotic or survival signaling pathways, which, in turn, resulted in tumor cell apoptosis. Taken together, our hypothesis that carbohydrate-binding motif evolution may impact the G. nivalis agglutinin-related lectin-induced survival or anti-apoptotic pathways would provide a new perspective for further elucidating the intricate relationships between the carbohydrate-binding specificities and complex molecular mechanisms by which G. nivalis agglutinin-related lectins induce cancer cell death.

• Authors: Qi-Jia Yu, Zi-Yue Li, Shun Yao, Miao Ming, Shu-Ya Wang, Bo Liu, Jin-Ku Bao
• Journal: Applied biochemistry and biotechnology (Appl Biochem Biotechnol) Vol. 165 Issue 3-4 Pg. 1037-46 (Oct 2011) ISSN: 1559-0291 [Electronic] United States
• PMID: 21748493 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hexosamines
• Hexoses
• Lectins, C-Type
• Mannose Receptor
• Mannose-Binding Lectins
• Neoplasm Proteins
• Plant Lectins
• Receptors, Cell Surface
• snowdrop lectin
• N-Acetylneuraminic Acid

Topics

• Amino Acid Motifs
• Binding Sites
• Cell Death (drug effects)
• Computer Simulation
• Conserved Sequence
• Evolution, Molecular
• Galanthus (chemistry)
• Hexosamines (chemistry, metabolism)
• Hexoses (chemistry, metabolism)
• Humans
• Lectins, C-Type (chemistry, metabolism)
• Mannose Receptor
• Mannose-Binding Lectins (chemistry, metabolism, pharmacology)
• Models, Molecular
• N-Acetylneuraminic Acid (chemistry, metabolism)
• Neoplasm Proteins (chemistry, metabolism)
• Neoplasms (drug therapy, pathology)
• Phylogeny
• Plant Lectins (chemistry, metabolism, pharmacology)
• Protein Binding
• Protein Structure, Tertiary
• Receptors, Cell Surface (chemistry, metabolism)
• Signal Transduction
• Tumor Cells, Cultured