InterPro domain: IPR028614

GDP-L-fucose synthase is responsible for the last step of the major metabolic pathway resulting in GDP-L-fucose synthesis from GDP-D-mannose. It catalyses a combined epimerase and NADPH-dependent reductase reaction, converting GDP-4-keto-6-D-deoxymannose to GDP-L-fucose [ 1 ]. Since several cell-surface antigens, including the leukocyte Lewis system and cell-surface antigens in pathogenic bacteria, depend on the availability of GDP-L-fucose for their expression, the enzyme is a potential target for therapy in pathological states depending on selectin-mediated cell-to-cell interactions [ 2 ].

This entry also includes ColC from Yersinia pseudotuberculosis. ColC is a GDP-L-colitose synthase, which is a bifunctional enzyme catalysaing the C-5 epimerization of GDP-4-keto-3,6-dideoxy-D-mannose and the subsequent C-4 keto reduction of the resulting L-epimer to give GDP-L-colitose [ 3 ].

1. Synthesis of GDP-L-fucose by the human FX protein. J. Biol. Chem. 271, 27274-9
2. Probing the catalytic mechanism of GDP-4-keto-6-deoxy-d-mannose Epimerase/Reductase by kinetic and crystallographic characterization of site-specific mutants. J. Mol. Biol. 303, 77-91
3. Biosynthesis of colitose: expression, purification, and mechanistic characterization of GDP-4-keto-6-deoxy-D-mannose-3-dehydrase (ColD) and GDP-L-colitose synthase (ColC). Biochemistry 43, 16450-60