GDP-L-fucose synthase

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
Search PMC articles PubMed articles NCBI proteins

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⁺${\displaystyle \rightleftharpoons }$ GDP-L-fucose + NADP⁺

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.

See also

• Guanosine diphosphate
• Guanosine diphosphate mannose

References

1. University of Zurich (2018, October 11). Link Between Gut Flora and Multiple Sclerosis Discovered. NeuroscienceNews. Retrieved October 11, 2018
2. 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.