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 15N-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.
Original language | English (US) |
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Pages (from-to) | 543-551 |
Number of pages | 9 |
Journal | Glycobiology |
Volume | 22 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2012 |
Bibliographical note
Funding Information:This work has been supported by a research grant from the National Cancer Institute (NIH R01 CA096090) to KHM. MCM was supported by the Cancer Biology Training Grant to the University of Minnesota from the National Institutes of Health (NIH T32 CA009138). NMR instrumentation was provided with funds from the National Science Foundation (BIR-961477), the University of Minnesota Medical School and the Minnesota Medical Foundation.
Keywords
- NMR
- galactose
- glycan
- lectin
- protein