Disease relevance of guanosine diphosphomannose

• GDPmannose dehydrogenase and biosynthesis of alginate-like polysaccharide in a mucoid strain of Pseudomonas aeruginosa [1].
• The genes rfbK and rfbM from the rfb cluster (O-antigen biosynthesis) of Salmonella enterica, group B, encoding for the enzymes phosphomannomutase (EC 5.4.2.8) and GDP-alpha-D-mannose pyrophosphorylase (EC 2.7.7.13) were overexpressed in E.coli BL21 (DE3) with specific activities of 0.1 U/mg and 0.3-0.6 U/mg, respectively [2].
• By using the same expression system, GDPmannose dehydrogenase activity was detected in both P. aeruginosa and E. coli [3].
• Two of the gene products showed 60-70% identity to the RfbM and RfbK proteins that are biosynthetic enzymes for the GDPmannose pathway of enterobacteria [4].
• The algD gene encodes NAD-linked GDPmannose dehydrogenase, which is essential for the mucoid phenotype, an important virulence factor expressed by Pseudomonas aeruginosa in cystic fibrosis patients [5].

High impact information on guanosine diphosphomannose

• Topography of glycosylation in yeast: characterization of GDPmannose transport and lumenal guanosine diphosphatase activities in Golgi-like vesicles [6].
• Essential steps in this process are thought to include transport of GDPmannose from the cytoplasm into the lumen of Golgi vesicles, transfer of mannose to glycoprotein acceptors, hydrolysis of the resulting GDP to GMP, and return of GMP and inorganic phosphate to the cytoplasm [6].
• To analyze the mechanisms leading to the emergence of mucoid P. aeruginosa in CF lungs, control of the algD gene coding for GDPmannose dehydrogenase was studied [7].
• Expression, purification and characterization of recombinant phosphomannomutase and GDP-alpha-D-mannose pyrophosphorylase from Salmonella enterica, group B, for the synthesis of GDP-alpha-D-mannose from D-mannose [2].
• Transcriptional activation of the P. aeruginosa algD gene, which encodes GDPmannose dehydrogenase, is essential for alginate synthesis [8].

Biological context of guanosine diphosphomannose

• A protein fusion of the Pseudomonas aeruginosa algD gene, coding for GDPmannose dehydrogenase, and the truncated xylE gene cassette was used to verify the putative coding region and translational signals predicted from the algD nucleotide sequence [9].

Anatomical context of guanosine diphosphomannose

• The concentrations of GTP and GDP-alpha-D-mannose in lymph node extracts were determined to be 0.095 and 0.012 mumol per g, respectively [10].
• When radioactive Dol-PP-di-N-acetylchitobiose is incubated with yeast membranes in the presence of non-radioactive GDPmannose a small amount of a larger lipid oligosaccharides is formed besides the previously-described Dol-PP-(GlcNAc)2 mannose [11].
• GDPmannose dolicholphosphate mannosyltransferase of chicken liver mitochondria [12].
• Properties of the dolichol phosphate: GDPmannose mannosyltransferase of liver microsomes [13].
• Plasma membrane fractions from rat liver exhibited glycosyltransferase activity with endogenous membrane-associated acceptors and either UDP-galactose, UDPglucose, UDP-N-acetylglucosamine, or GDPmannose donors [14].

Associations of guanosine diphosphomannose with other chemical compounds

• 8 kDa homodimer which, in the presence of Mg(2+), catalyzes the hydrolysis of GDP-alpha-D-mannose or GDP-alpha-D-glucose to yield sugar and GDP [15].
• Homogenates of adult Dirofilaria immitis possess a microsomal enzyme system able to transfer mannose from GDPmannose to endogenous lipid intermediate(s) and exogenous dolichol monophosphate [16].

Gene context of guanosine diphosphomannose

• Gene algD coding for GDPmannose dehydrogenase is transcriptionally activated in mucoid Pseudomonas aeruginosa [3].
• Topological orientation of mitochondrial GDPmannose: dolichyl-monophosphate mannosyltransferase in the outer membrane [17].

Analytical, diagnostic and therapeutic context of guanosine diphosphomannose

• The disaccharides formed by incubation of dolichyl mannosyl phosphate or GDPmannose with mannose were identified by paper chromatography and electrophoresis as mannose-alpha-1,2-mannose and mannose-alpha-1,3-mannose. synthesis of each product was dependent on the assay conditions used and was most markedly affected by the presence of detergent [18].

References