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    • "Despite extensive research, only very few endogenous ligands for TLR4 have been described so far (Chen and Nuñ ez, 2010). Galectins represent a protein family with at least 15 members that have significant sequence similarity in their carbohydraterecognition domain (CRD) and bind to b-galactosides with varying affinities and specificities (Barondes et al., 1994; Leffler et al., 2004). Galectins are classified into three subgroups (1) proto, (2) chimera, and (3) tandem repeat based on their molecular architecture . "
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    ABSTRACT: Graphical Abstract Highlights d Gal3 acts as an endogenous TLR4 ligand with a Kd value around 1 mM d Gal3 can initiate a TLR4-dependent inflammatory response in microglia d Gal3 is required for complete activation of TLR4 upon LPS treatment d Gal3-TLR4 interaction is confirmed in vivo and in stroke patients In Brief In this publication, Burguillos et al. demonstrate how galectin-3 (Gal3) released from reactive microglia cells can activate other surrounding immune cells in a paracrine manner by binding to and activating Toll-like receptor 4 (TLR4). This finding could explain the propagation of the inflammatory response once the initial stimulus is gone.
    Cell Reports 04/2015; 10(9):1626-1638. DOI:10.1016/j.celrep.2015.02.012 · 8.36 Impact Factor
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    • "Classifications and the detailed structural and functional information of lectins are available in the widely distributed databases and literatures (Sharon and Lis, 2004; Chandra et al., 2006; Damodaran et al., 2008; Pérez et al., 2014). Galectins (previously termed S-type lectins) are β-galactoside binding proteins which have at least one carbohydrate recognition domain and certain conserved sequence elements (Barondes et al., 1994a, 1994b; Cummings and Liu, 2009). Galectins have the ability to serve as potent antitumors and cancer biomarkers as they induce tumor cell apoptosis (Kim et al., 1993; Hengartner, 2000; Rabinovich, 2005; Yang et al., 2005; Yang et al., 2009; Balan et al., 2010). "
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    ABSTRACT: Galectins are β-galactoside binding proteins which have the ability to serve as potent antitumor, cancer biomarker, and induce tumor cell apoptosis. Agrocybe cylindracea galectin (ACG) is a fungal galectin which specifically recognizes α(2,3)-linked sialyllactose at the cell surface that plays extensive roles in the biological recognition processes. To investigate the change in glycan-binding specificity upon mutations, single point and double point site-directed in silico mutations are performed at the binding pocket of ACG. Molecular dynamics (MD) simulation studies are carried out for the wild-type (ACG) and single point (ACG1) and double point (ACG2) mutated ACGs to investigate the dynamics of substituted mutants and their interactions with the receptor sialyllactose. Plausible binding modes are proposed for galectin-sialylglycan complexes based on the analysis of hydrogen bonding interactions, total pair-wise interaction energy between the interacting binding site residues and sialyllactose and binding free energy of the complexes using molecular mechanics-Poisson-Boltzmann surface area. Our result shows that high contribution to the binding in different modes is due to the direct and water-mediated hydrogen bonds. The binding specificity of double point mutant Y59R/N140Q of ACG2 is found to be high, and it has 26 direct and water-mediated hydrogen bonds with a relatively low-binding free energy of -47.52 ± 5.2 kcal/mol. We also observe that the substituted mutant Arg59 is crucial for glycan-binding and for the preference of α(2,3)-linked sialyllactose at the binding pocket of ACG2 galectin. When compared with the wild-type and single point mutant, the double point mutant exhibits enhanced affinity towards α(2,3)-linked sialyllactose, which can be effectively used as a model for biological cell marker in cancer therapeutics. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
    Journal of Molecular Recognition 03/2015; 28(9). DOI:10.1002/jmr.2468 · 2.15 Impact Factor
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    • "Abbott and Feizi (1991) reported that the consistency in the short loops structure among the galectins exhibit their proteolytic stability which is necessary for the sugar binding activity. CsGal-1 occurs as a monomer as well as a non-covalent homodimer that consists of a single CRD as reported by Barondes et al. (1994a) and Cho and Cummings (1995). Lopez-Lucendo et al. (2004) and Camby et al. (2006) suggested that the integrity of the dimer is maintained by the interactions between the monomers of galectin as well as the stability of the dimerization interface in the galectin. "
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    ABSTRACT: In this study, we reported a molecular characterization of a novel proto-type galectin-1 from the striped murrel Channa striatus (named as CsGal-1). The full length CsGal-1 was identified from an established striped murrel cDNA library and further we confirmed the sequence by cloning. The complete cDNA sequence of CsGal-1 is 590 base pairs (bp) in length and its coding region encoded a poly peptide of 135 amino acids. The polypeptide contains a galactoside binding lectin domain at 4-135. The domain carries a sugar binding site at 45-74 along with its signatures (H45-X-Asn47-X-Arg49 and Trp69-X-X-Glu72-X-Arg74). CsGal-1 shares a highly conserved carbohydrate recognition domain (CRD) with galectin-1 from other proto-type galectin of teleosts. The mRNA expressions of CsGal-1 in healthy and various immune stimulants including Aphanomyces invadans, Aeromonas hydrophila, Escherchia coli lippopolysaccharde and poly I:C injected tissues of C. striatus were examined using qRT-PCR. CsGal-1 mRNA is highly expressed in kidney and is up-regulated with different immune stimulants at various time points. To understand its biological activity, the coding region of CsGal-1 gene was expressed in an E. coli BL21 (DE3) cloning system and its recombinant protein was purified. The recombinant CsGal-1 protein was agglutinated with mouse erythrocytes at a concentration of 4 μg/mL in a calcium independent manner. CsGal-1 activity was inhibited by D-galactose at 25 mM−1and D-glucose and D-fructose at 100 mM−1. The results of microbial binding assay showed that the recombinant CsGal-1 protein agglutinated only with the Gram-negative bacteria. Interestingly, we observed no agglutination against Gram-positive bacteria. Overall, the study showed that CsGal-1 is an important immune gene involved in the recognition and elimination of pathogens in C. striatus.
    Microbiological Research 11/2014; 169(11). DOI:10.1016/j.micres.2014.03.005 · 2.56 Impact Factor
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