期刊
GLYCOBIOLOGY
卷 22, 期 4, 页码 543-551出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/glycob/cwr173
关键词
galactose; glycan; lectin; NMR; protein
资金
- National Cancer Institute [NIH R01 CA096090]
- National Institutes of Health [NIH T32 CA009138]
- National Science Foundation [BIR-961477]
- University of Minnesota Medical School
- Minnesota Medical Foundation
Galectins have a highly conserved carbohydrate-binding domain to which a variety of galactose-containing saccharides, both beta- and alpha-galactosides, can interact with varying degrees of affinity. Recently, we demonstrated that the relatively large alpha(1 -> 6)-d-galacto-beta(1 -> 4)-d-mannan (Davanat) binds galectin-1 (gal-1) primarily at an alternative carbohydrate-binding domain. Here, we used a series of alpha-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 N-15-labeled gal-1 and statistical modeling suggest that the optimal signature consists of alpha-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 beta-galactoside-binding region. The use of two small, well-defined GMs [6(1)-alpha(1 -> 6)-d-galactosyl-beta-d-mannotriaose and 6(3),6(4)-di-alpha(1 -> 6)-d-galactosyl-beta-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.
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