Composition of Drosophila melanogaster Proteome Involved in Fucosylated Glycan Metabolism

Abstract

The whole genome approach enables the characterization of all components of any given biological pathway. Moreover, it can help to uncover all the metabolic routes for any molecule. Here we have used the genome of Drosophila melanogaster to search for enzymes involved in the metabolism of fucosylated glycans. Our results suggest that in the fruit fly GDP-fucose, the donor for fucosyltransferase reactions, is formed exclusively via the de novo pathway from GDP-mannose through enzymatic reactions catalyzed by GDP-D-mannose 4,6-dehydratase (GMD) and GDP-4-keto-6-deoxy-Dmannose 3,5-epimerase/4-reductase (GMER, also known as FX in man). The Drosophila genome does not have orthologs for the salvage pathway enzymes, i.e. fucokinase and GDP-fucose pyrophosphorylase synthesizing GDP-fucose from fucose. In addition we identified two novel fucosyltransferases predicted to catalyze ␣1,3-and ␣1,6-specific linkages to the GlcNAc residues on glycans. No genes with the capacity to encode ␣1,2-specific fucosyltransferases were found. We also identified two novel genes coding for O-fucosyltransferases and a gene responsible for a fucosidase enzyme in the Drosophila genome. Finally, using the Drosophila CG4435 gene, we identified two novel human genes putatively coding for fucosyltransferases. This work can serve as a basis for further whole-genome approaches in mapping all possible glycosylation pathways and as a basic analysis leading to subsequent experimental studies to verify the predictions made in this work.

Dysregulation of TGF-β1 receptor activation leads to abnormal lung development and emphysema-like phenotype in core fucose-deficient mice

“…5, which is published as supporting information on the PNAS web site). This finding agrees with previous reports indicating that there are no additional genes homologous to Fut8 in mammals and lower organisms (21,22). Thus, the Fut8 gene is the only one responsible for the core fucosylation of N-glycans in mouse tissues.…”

Structure of the MUR1 GDP-Mannose 4,6-Dehydratase from Arabidopsis thaliana: Implications for Ligand Binding and Specificity

“…The proposed mechanism for the MUR1 reaction (68) is shown schematically in Figure 1. In the first step, common to all SDR enzymes, the deprotonation of the O4 hydroxyl by a general base, coupled with concerted hydride abstraction from the C4 atom by the NAD(P) + cofactor, yields a 4-keto intermediate (2). The MUR1 reaction then proceeds by elimination of a water molecule from C6, yielding a 4-keto-5,6-ene species (3), followed by reduction of the C5-C6 double bond to form the final 4-keto-6-deoxymannose product (4).…”

“…In humans, L-fucose is most notably an important constituent of glycoproteins such as the blood group antigens as well as cell surface carbohydrate ligands of the cell adhesion family of selectins involved in functions such as inflammation and the immune response (1). Among other organisms, L-fucosecontaining glycoconjugates are involved in developmental signaling in Drosophila (2), are critical components of bacterial cell walls where they may play a role in pathogenicity, and among rhizobial organisms, are components of Nod factors, influencing nodulation efficiency and host specificity (3,4). In plants, L-fucose has important structural functions as a component of glycoproteins and cell wall polysaccharides, such as xyloglucan and rhamnogalacturonans I and II.…”

The Drosophila Neurally Altered Carbohydrate Mutant Has a Defective Golgi GDP-fucose Transporter

“…1A). GDP-fucose is produced in the cytoplasm (27) and transported into the Golgi apparatus by GFR, a specific GDP-fucose transporter, in exchange for GMP (Fig. 1A) (28,29).…”