GDP-L-Fucose Synthase (human, recombinant)

GDP-L-Fucose synthase, encoded by the gene TSTA3, is an NADP(H)-binding protein that catalyzes the final step in the synthesis of GDP-L-fucose from GDP-D-mannose.^1,2 It converts GDP-4-keto-6-deoxy-D-mannose to GDP-L-fucose via a two-step reaction consisting of epimerization followed by NADPH-dependent reduction. GDP-L-Fucose synthase exists as a homodimer and is comprised of an N-terminal NADPH-binding domain and a C-terminal substrate-binding domain. TSTA3^-/- mice exhibit increases in colonic inflammation, dysplasia, and epithelial permeability, which are reversed following addition of fucose to the diet.³ These mice also exhibit alterations in gut microflora and increased bacterial burden in colon transluminal tissue and feces when fed a normal diet versus a fucose-supplemented diet, and the colonic effects of TSTA3 deletion can be reversed following administration of antibiotics. GDP-L-Fucose synthase has been identified as an autoantigen that can be recognized by CD4⁺ T cells derived from patients with multiple sclerosis.⁴ Expression of GDP-L-fucose synthase in primary tumor tissue samples from patients with esophageal squamous cell carcinoma (ESCC) positively correlates with increased clinical stage, lymph node metastasis, and poor prognosis.⁵

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1. Tonetti, M., Sturla, L., Bisso, A., et al. Synthesis of GDP-L-fucose by the human FX protein. The Journal of Biological Chemisty 271(44), 27274-27279 (1996).

2. Zhou, H., Sun, L., Li, J., et al. The crystal structure of human GDP-L-fucose synthase. Acta Biochim. Biophys. Sin. (Shanghai) 45(9), 720-725 (2013).

3. Wang, Y., Huang, D., Chen, K.-Y., et al. Fucosylation deficiency in mice leads to colitis and adenocarcinoma. Gastroenterology 152(1), 193-205 (2017).

4. Planas, R., Santos, R., Tomas-Ojer, P., et al. GDP-L-fucose synthase is a CD4⁺ T cell-specific autoantigen in DRB3*02:02 patients with multiple sclerosis. Sci. Transl. Med. 10(462), eaat4301 (2018).

5. Yang, J., Kong, P., Yang, J., et al. High TSTA3 expression as a candidate biomarker for poor prognosis of patients with ESCC. Technol. Cancer Res. Treat. 17, 1533033818781405 (2018).