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Publication Abstract from PubMed

alpha-L-fucosyl residues attached at the non-reducing ends of glycoconjugates constitute histo-blood group antigens Lewis (Le) and ABO and play fundamental roles in various biological processes. Therefore, establishing a method for synthesizing the antigens is important for functional glycomics studies. However, regiospecific synthesis of glycosyl linkages, especially alpha-L-fucosyl linkages, is quite difficult to control both by chemists and enzymologists. Here, we generated an alpha-L-fucosynthase that specifically introduces Le(a) and Le(x) antigens into the type-1 and type-2 chains, respectively; i.e. the enzyme specifically accepts the disaccharide structures (Galbeta1-3/4GlcNAc) at the non-reducing ends and attaches a Fuc residue via an alpha-(1,4/3)-linkage to the GlcNAc. X-ray crystallographic studies revealed the structural basis of this strict regio- and acceptor specificity, which includes the induced fit movement of the catalytically important residues, and the difference between the active site structures of 1,3-1,4-alpha-L-fucosidase (EC 3.2.1.111) and alpha-L-fucosidase (EC 3.2.1.51) in glycoside hydrolase family 29. The glycosynthase developed in this study should serve as a potentially powerful tool to specifically introduce the Le(a/x) epitopes onto labile glycoconjugates including glycoproteins. Mining glycosidases with strict specificity may represent the most efficient route to the specific synthesis of glycosidic bonds.

1,3-1,4-alpha-L-fucosynthase that specifically introduces Lewis a/x antigens into type-1/2 chains.,Sakurama H, Fushinobu S, Hidaka M, Yoshida E, Honda Y, Ashida H, Kitaoka M, Kumagai H, Yamamoto K, Katayama T J Biol Chem. 2012 May 11;287(20):16709-19. Epub 2012 Mar 26. PMID:22451675^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.