National Center for
4J28: Crystal Structure of a Gh29 Alpha-l-fucosidase Gh29 From Bacteroides Thetaiotaomicron in Complex With a 5-membered Iminocyclitol Inhibitor
Three dimensional structure of a bacterial alpha-l-fucosidase with a 5-membered iminocyclitol inhibitor
Bioorg. Med. Chem. (2013) 21 p.4751-4754
Fucosidases, enzymes that cleave fucose from the non-reducing end of a glycan, represent promising medicinal targets reflecting their roles in cancer metastasis, inflammation, host-parasite interactions and the lysosomal storage disorder fucosidosis. The X-ray crystal structures of Bacteroides thetaiotaomicron GH29 alpha-l-fucosidase (BtFuc2970) in a new crystal form (at a resolution of 1.59A) and liganded with a 5-membered iminocyclitol inhibitor (1.73A) are reported herein. The 5-membered iminocyclitol binds in a (3)E conformation, mimicking the proposed (3)H4 half chair transition-state of the enzyme catalysed reaction, and its Ki for BtFuc2970 was determined as 2muM. Structural analysis of fucosidase inhibition through 5-membered iminocyclitols will aid in the rational design of more potent fucosidase inhibitors for treatment of a range of medical conditions.