Trichoderma reesei alpha-1,2-mannosidase: Structural basis for the cleavage of four consecutive mannose residues

The process of N-glycosylation of eukaryotic proteins involves a range of h ost enzymes that delete or add saccharide monomers. While endoplasmic retic ulum (E.R.) mannosidases cleave only one mannose to produce the Man8B isome r, an alpha -1,2-mannosidase from Trichoderma reesei can sequentially cleav e all four 1,2-linked mannose sugars from a Man(9)GlcNAc(2) oligosaccharide , a feature reminiscent of the activity of Golgi mannosidases. We now repor t the structure of the T. reesei enzyme at 2.37 Angstrom resolution. The en zyme folds as an (alpha alpha)(7) barrel. The substrate-binding site of the T. reesei mannosidase differs appreciably from the Saccharomyces cerevisia e enzyme. In the former, shorter loops at the surface allow substrate prote in to come closer to the catalytic site. There is more internal space avail able, so that different oligosaccharide conformations are sterically allowe d in the T. reesei alpha -1,2-mannosidase. (C) 2001 Academic Press.