Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Chemical Compound Review:

CHEBI:16955 [(2R,3S,4R,5R)-5-(2-amino-6- oxo-3H-purin-9...

Synonyms: HMDB01346, AC1L97D8, C01222, 18186-48-6, GDP-4-dehydro-D-rhamnose, ...

Albermann, C. et al., Tonetti, M. et al., Mäki, M. et al., Bulet, P. et al., Webb, N.A. et al., et al.

Sullivan, Kumar, Kriz, Stahl, Xu, Rouse, Chang, Boodhoo, Potvin, Cumming,

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Disease relevance of C01222

The biosynthetic pathway of GDP-L-fucose starts with a dehydration of GDP-D-mannose catalyzed by GDP-D-mannose 4,6-dehydratase (Gmd) creating GDP-4-keto-6-deoxymannose which is subsequently converted by the GDP-4-keto-6-deoxy-D-mannose 3,5-epimerase-4-reductase (WcaG; GDP-beta-L-fucose synthetase) to GDP-beta-L-fucose [1].
Preliminary crystallographic investigations of recombinant GDP-4-keto-6-deoxy-D-mannose epimerase/reductase from E. coli [2].
Functional expression of Pseudomonas aeruginosa GDP-4-keto-6-deoxy-D-mannose reductase which synthesizes GDP-rhamnose [3].

High impact information on C01222

The biosynthesis of d-rhamnose proceeds through the conversion of GDP-d-mannose by GDP-d-mannose 4,6-dehydratase (GMD) to GDP-4-keto-6-deoxymannose, which is subsequently reduced to GDP-d-rhamnose by a reductase [4].
With the purified His-tag WcaG Km and Vmax values, respectively, of 40 microM and 23 nkat/mg protein for the substrate GDP-4-keto-6-deoxy-D-mannose and of 21 microM and 10 nkat/mg protein for the cosubstrate NADPH were obtained; a pH optimum of 7.5 was determined and the enzyme was stimulated to equal extend by the divalent cations Mg2+ and Ca2+ [1].
It is first converted by the GDP-mannose-4,6-dehydratase (GMD) into GDP-4-keto-6-deoxy-D-mannose, and then reduced to GDP-D-rhamnose by GDP-4-keto-6-deoxy-D-mannose reductase (RMD) [3].
The GDP-4-keto-6-deoxy-D-mannose epimerase/reductase (GM_ER) isolated from E. coli has been overexpressed as a GST-fusion protein and purified to homogeneity [2].
GM_ER shows significant structural homology to the human erythrocyte protein FX, which is involved in blood-group glycoconjugate biosynthesis, displaying 3,5 epimerase/reductase activity on GDP-4-keto-6-deoxy-D-mannose [2].

Gene context of C01222

This conversion is a multi-step reaction as proved by the involvement of two intermediates identified as GDP-4-oxo-6-deoxy-D-mannose and GDP-4-oxo-6-deoxy-L-galactose, this latter being reduced by NADPH to give GDP-L-fucose [5].
The 'de novo' pathway of GDP-L-fucose biosynthesis from GDP-D-mannose involves a GDP-D-mannose 4,6 dehydratase (GMD) and a GDP-4-keto-6-deoxy-D-mannose epimerase/reductase (GMER) [6].

Analytical, diagnostic and therapeutic context of C01222

We have isolated the product of the dehydratase reaction, GDP-4-keto-6-deoxymannose, and confirmed its structure by electrospray ionization-mass spectrometry and high field NMR [7].

References

Preparative synthesis of GDP-beta-L-fucose by recombinant enzymes from enterobacterial sources. Albermann, C., Distler, J., Piepersberg, W. Glycobiology (2000) [Pubmed]
Preliminary crystallographic investigations of recombinant GDP-4-keto-6-deoxy-D-mannose epimerase/reductase from E. coli. Tonetti, M., Rizzi, M., Vigevani, P., Sturla, L., Bisso, A., De Flora, A., Bolognesi, M. Acta Crystallogr. D Biol. Crystallogr. (1998) [Pubmed]
Functional expression of Pseudomonas aeruginosa GDP-4-keto-6-deoxy-D-mannose reductase which synthesizes GDP-rhamnose. Mäki, M., Järvinen, N., Räbinä, J., Roos, C., Maaheimo, H., Renkonen, R. Eur. J. Biochem. (2002) [Pubmed]
Crystal structure of a tetrameric GDP-D-mannose 4,6-dehydratase from a bacterial GDP-D-rhamnose biosynthetic pathway. Webb, N.A., Mulichak, A.M., Lam, J.S., Rocchetta, H.L., Garavito, R.M. Protein Sci. (2004) [Pubmed]
Study of the conversion of GDP-mannose into GDP-fucose in Nereids: a biochemical marker of oocyte maturation. Bulet, P., Hoflack, B., Porchet, M., Verbert, A. Eur. J. Biochem. (1984) [Pubmed]
GDP-4-keto-6-deoxy-D-mannose epimerase/reductase from Escherichia coli, a key enzyme in the biosynthesis of GDP-L-fucose, displays the structural characteristics of the RED protein homology superfamily. Rizzi, M., Tonetti, M., Vigevani, P., Sturla, L., Bisso, A., Flora, A.D., Bordo, D., Bolognesi, M. Structure (1998) [Pubmed]
Molecular cloning of human GDP-mannose 4,6-dehydratase and reconstitution of GDP-fucose biosynthesis in vitro. Sullivan, F.X., Kumar, R., Kriz, R., Stahl, M., Xu, G.Y., Rouse, J., Chang, X.J., Boodhoo, A., Potvin, B., Cumming, D.A. J. Biol. Chem. (1998) [Pubmed]

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