GDP-L-fucose synthase
In enzymology, a GDP-L-fucose synthase (EC 1.1.1.271) is an enzyme that catalyzes the chemical reaction
- GDP-4-dehydro-6-deoxy-D-mannose + NADPH + H+ GDP-L-fucose + NADP+
| GDP-L-fucose synthase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC no. | 1.1.1.271 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
| |||||||||
Thus, the three substrates of this enzyme are GDP-4-dehydro-6-deoxy-D-mannose, NADPH, and H+, whereas its two products are GDP-L-fucose and NADP+.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is GDP-L-fucose:NADP+ 4-oxidoreductase (3,5-epimerizing). This enzyme is also called GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase. This enzyme participates in fructose and mannose metabolism.
Relevance in diseases
It has been reported that some cases of multiple sclerosis that present the HLA variant DRB3, present also autoimmunity against GDP-L-fucose synthase.[1][2] The same report points out that the autoimmune problem could derive from the gut microbiota.
References
- University of Zurich (2018, October 11). Link Between Gut Flora and Multiple Sclerosis Discovered. NeuroscienceNews. Retrieved October 11, 2018
- R. Planas et al, GDP-l-fucose synthase is a CD4+ T cell–specific autoantigen in DRB3*02:02 patients with multiple sclerosis, Science Translational Medicine 10 Oct 2018, Vol. 10, Issue 462, eaat4301, DOI: 10.1126/scitranslmed.aat4301
- Chang S, Duerr B, Serif G (1988). "An epimerase-reductase in L-fucose synthesis". J. Biol. Chem. 263 (4): 1693–7. PMID 3338988.
- Mattila P, Rabina J, Hortling S, Helin J, Renkonen R (2000). "Functional expression of Escherichia coli enzymes synthesizing GDP-L-fucose from inherent GDP-D-mannose in Saccharomyces cerevisiae". Glycobiology. 10 (10): 1041–7. doi:10.1093/glycob/10.10.1041. PMID 11030750.
- Menon S, Stahl M, Kumar R, Xu GY, Sullivan F (1999). "Stereochemical course and steady state mechanism of the reaction catalyzed by the GDP-fucose synthetase from Escherichia coli". J. Biol. Chem. 274 (38): 26743–50. doi:10.1074/jbc.274.38.26743. PMID 10480878.
- Somers WS, Stahl ML, Sullivan FX (1998). "GDP-fucose synthetase from Escherichia coli: structure of a unique member of the short-chain dehydrogenase/reductase family that catalyzes two distinct reactions at the same active site". Structure. 6 (12): 1601–12. doi:10.1016/S0969-2126(98)00157-9. PMID 9862812.