title: Structural features for α-galactomannan binding to galectin-1.
abstract: Galectins have a highly conserved carbohydrate-binding domain to which a variety of galactose-containing saccharides, both β- and α-galactosides, can interact with varying degrees of affinity. Recently, we demonstrated that the relatively large α(1 → 6)-D-galacto-β(1 → 4)-D-mannan (Davanat) binds galectin-1 (gal-1) primarily at an alternative carbohydrate-binding domain. Here, we used a series of α-galactomannans (GMs) that vary in their mannose-to-galactose ratios for insight into an optimal structural signature for GM binding to gal-1. Heteronuclear single-quantum coherence nuclear magnetic resonance spectroscopy with (15)N-labeled gal-1 and statistical modeling suggest that the optimal signature consists of α-D-galactopyranosyl doublets surrounded by regions of about four or more "naked" mannose residues. These relatively large and complex GMs all appear to interact with varying degrees at essentially the same binding surface on gal-1 that includes the Davanat alternative binding site and elements of the canonical β-galactoside-binding region. The use of two small, well-defined GMs [6(1)-α(1 → 6)-D-galactosyl-β-D-mannotriaose and 6(3),6(4)-di-α(1 → 6)-D-galactosyl-β-D-mannopentaose] helped characterize how GMs, in general, interact in part with the canonical site. Overall, our findings contribute to better understanding interactions of gal-1 with larger, complex polysaccharides and to the development of GM-based therapeutics for clinical use.
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics,  University of Minnesota Health Sciences Center, 6-155 Jackson Hall, 321 Church Street, Minneapolis, MN 55455,  USA.
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Miller
authors.forename: Anatole A
authors.initials: AA
authors.lastname: Klyosov
authors.forename: Kevin H
authors.initials: KH
authors.lastname: Mayo
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D002236:Carbohydrate Conformation; D015195:Drug Design; D005690:Galactose / Q000031:analogs & derivatives; D037483:Galectin 1 / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008351:Mannans / Q000737:chemistry*; D008958:Models, Molecular; D009844:Oligosaccharides / Q000737:chemistry; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D014312:Trisaccharides / Q000737:chemistry
chemical_list: D037483:Galectin 1; C445499:LGALS1 protein, human; D008351:Mannans; D009844:Oligosaccharides; D014312:Trisaccharides; C012990:galactomannan; C023872:mannotriose; C048068:mannopentaose; D005690:Galactose