Investigation on the binding specificity of Agrocybe cylindracea galectin towards α(2,6)-linked sialyllactose by molecular modeling and molecular dynamics simulations

Abstract

Galectins are β-galactoside binding proteins that act as potential cancer biomarkers. Agrocybe cylindracea galectin (ACG) is a fungal galectin which recognizes specifically α(2,3)-linked sialyllactose and play a pivotal role in biological recognition processes. This manuscript has presented the theoretical investigation on enhancing the binding specificity of ACG towards α(2,6)-linked sialyllactose. In silico single point and double point mutations were carried out at the binding site amino acid residues of ACG to enhance its binding to α(2,6)-linked sialyllactose, and the mutated protein-carbohydrate complexes were simulated for 30 ns durations. Analysis of the interaction patterns of the carbohydrate at the binding site of wild type and mutated lectins revealed that sialic acid contributed more to the binding when compared with other sugar units in the trisaccharide and enhanced the binding specificity of ACG towards α(2,6)-linked sialyllactose.

Graphical Abstract

Theoretical investigation on the glycan-binding specificity of Agrocybe cylindracea galectin towards α(2,6)-linked sialyllactose.

KEYWORDS:

• Fungal galectin
• sialyllactose
• molecular dynamics
• lectin-carbohydrate interaction
• binding specificity

Acknowledgments

Ponnusamy Parasuraman, Jeyasigamani F A Selvin, and Kasinadar Veluraja acknowledge the use of DBT funded Bioinformatics Infrastructure Facility (BIF) hosted at the Department of Biotechnology, Manonmaniam Sundaranar University, Tamil Nadu, India for simulations.

Additional information

Funding

The authors acknowledge the Department of Biotechnology (DBT), Ministry of Science & Technology, India and National Institute of Advanced Industrial Science and Technology (AIST), Japan for financial support.