Evolutionary analysis of galectins and identification of potential galectin-1 inhibitors: A computational approach

Krishnan Anbarasu,Vipperla Bhavaniprasad,Sivaraman Jayanthi

doi:10.3329/bjp.v9i3.19716

Abstract

Galectins are a family of structurally related carbohydrate-binding proteins and some galectins play a major role in initiation, progression and dissemination of different types of tumors. Multiple sequence alignment was performed for 15 types of galectins and phylogenetic tree was constructed for studying evolutionary relationship. Among galectins, galectin-1 contributes to various events associated with cancer biology including tumor transformation, cell cycle regulation and apoptosis. Hence a rational computational approach was followed for the design of new class of glycol-mimetic inhibitors with high affinity and stability. Ten N-39-triazole analogs have been used for molecular docking with galectin-1. Based on docking studies, hexaconazole is identified as a potential inhibitor of galectin-1 for the inhibition of the tumor activity. The binding mechanism of hexaconazole to galectin-1 in the dynamics system was studied by 10 ns Molecular Dynamics simulation. Thus, our study favors more insight on hexaconazole as a promising inhibitor for galectin-1.

Highlights

Galectin, a type of lectin, adheres the -galactoside
In order to identify the dominant motions of galectin-1, we have used principal component analysis method which takes the trajectory of a MD simulation and extracts the dominant modes involved in the motion of the molecule (Amadei et al, 1993)
The representing galectin-3 sequence from Homo sapiens is used as the reference sequence which falls under clade–II

Summary

Introduction

A type of lectin, adheres the -galactoside. The galectins comprise of a -galactoside adhering lectins bearing a homologous carbohydrate recognition domains (CRDs) (Ajit et al, 2009). The tandem repeat galectins comprising the galectin- 4, 8, 9, 12, include two CRDs and a single polypeptide linked by tiny peptide domain. Galectin-1 can function in both carbohydrate-dependent and independent manners either positive or negative depending on responder cell types or sub cellular localization (Rabinovich et al, 2002). The endogenous protein may function as a growth-promoting factor; exogenously added galectin-1 suppresses tumor cell proliferation (Mercier et al, 2008). Occurring carbohydrate ligands for galectins have low affinities, too polar and possess low physiological stabilities (Giguere et al, 2006). Some N-39-triazole analogs provided high affinity enhancement and can be considered as possible inhibitors for galectin-1 (Hope et al, 2008)

Materials and Methods

Results and Discussion

10 Albaconazole

Conclusion