Disease relevance of guanosine diphosphate mannose

• The GDP-mannose-dependent enzyme of R. leguminosarum may represent a functional equivalent of E. coli RfaC [1].
• Incubation of a membrane fraction from Mycobacterium smegmatis cells with GDP-mannose and free mannose at pH 7 in presence of Mg2+ ions resulted in the formation of a series of alpha 1----6-linked mannooligosaccharides with up to 12 mannoses [2].
• Allosterism and cooperativity in Pseudomonas aeruginosa GDP-mannose dehydrogenase [3].
• Transcription of algD, encoding GDP-mannose dehydrogenase, the key enzyme in the alginate biosynthetic pathway, is highly regulated in Azotobacter vinelandii [4].
• In this report a recombinant bifunctional phosphomannose isomerase/GDP-D-mannose pyrophosphorylase from Helicobacter pylori has been studied [5].

High impact information on guanosine diphosphate mannose

• Most patients show a deficiency of phosphomannomutase (PMM)8, an enzyme necessary for the synthesis of GDP-mannose [6].
• Disruption of mannose activation in Leishmania mexicana: GDP-mannose pyrophosphorylase is required for virulence, but not for viability [7].
• Rough microsomes from rat liver have been subjected to various treatments and incubated afterwards with UDP-N-acetyl-[14C]glucosamine and GDP-mannose in the presence of GTP (0.5 mM), or of other nucleotides [8].
• GONST1 complemented a GDP-mannose transport-defective yeast mutant (vrg4-2), and Golgi-rich vesicles from the complemented strain displayed increased GDP-mannose transport activity [9].
• Incubation of fibroblast extracts with [(14)C]GlcNAc(2)-PP-dolichol and GDP-mannose indicated a severely reduced activity of the beta 1,4-mannosyltransferase, elongating GlcNAc(2)-PP-dolichol to Man(1)GlcNAc(2)-PP-dolichol at the cytosolic side of the endoplasmic reticulum [10].

Chemical compound and disease context of guanosine diphosphate mannose

• Extracts of E. coli do not catalyze GDP-mannose-dependent glycosylation of Kdo2-lipid IVA, but they are active when ADP-mannose is substituted for GDP-mannose [1].
• The combined action of the MUR1 and GER1 gene products converts GDP-D-mannose to GDP-L-fucose in vitro demonstrating that this entire nucleotide-sugar interconversion pathway could be reconstituted using plant genes expressed in Escherichia coli [11].
• Consequently, rfbM is sufficient for the biosynthesis of GDP-mannose for both O antigen and capsular polysaccharide E. coli O9:K30 [12].
• Genetics of xanthan production in Xanthomonas campestris: the xanA and xanB genes are involved in UDP-glucose and GDP-mannose biosynthesis [13].
• A second plasmid harbors msg, a gene from Rhodothermus marinus that encodes mannosylglycerate synthase, which catalyzes the formation of 2-O-alpha-D-mannosyl-D-glycerate from GDP-mannose and endogenous glycerate [14].

Biological context of guanosine diphosphate mannose

• Our study demonstrates that GDP-mannose biosynthesis is not essential for Leishmania viability in culture, but constitutes a virulence pathway in these human pathogens [7].
• This enzyme provides GDP-mannose, which is used for cell wall carbohydrate biosynthesis and protein glycosylation as well as for AsA biosynthesis [15].
• Inactivation of PMI at the restrictive temperature of 37 degrees C prevents synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions and results in cell death [16].
• Mild acid hydrolysis of the 1/10.3 soluble material released water-soluble, neutral 14C-oligosaccharides which eluted from Sephadex G-50 in two or three peaks between the standards cytochrome c and GDP-mannose.. [17].
• Although the GDP-mannose donor was used in the crystallization experiments and the GDP moiety is bound tightly to the active site, the mannose is not visible in the electron density [18].

Anatomical context of guanosine diphosphate mannose

• The reaction is temperature and detergent sensitive and requires ATP, GDP-mannose, Mg2+, and Mn2+, and the product invertase remains associated with sedimentable membranes [19].
• An enzyme present in rabbit liver microsomes has been found to catalyze mannosyltransfer from GDP-mannose to exogenously added oligosaccharide-lipid acceptor resulting in the formation of an alpha-1,2-mannosyl-mannose linkage [20].
• The two-step reaction sequence carried out by thyroid enzymes which leads to the formation of an alpha-D-manno-pyranosyl-D-mannose linkage in exogenous acceptors by transfer of mannose from GDP-mannose through a beta-linked intermediate appears to involve a double inversion of anomeric configuration of this sugar [21].
• Vanadate-sensitive ATPase showed a similar pattern, whereas GDP-mannose dolichyl-phosphate mannosyltransferase, an enzyme attached to the endoplasmic reticulum, remained in the same position in the gradients, irrespective of the amount of concanavalin A associated with the plasma membrane [22].
• The enzyme makes available GMP as an antiporter to be coupled with entry of GDP-mannose into the Golgi lumen from the cytosol [23].

Associations of guanosine diphosphate mannose with other chemical compounds

• We have cloned the cDNA encoding human GDP-mannose 4,6-dehydratase, the first enzyme in the pathway converting GDP-mannose to GDP-fucose [24].
• The data obtained indicate FX as the enzyme responsible for the last step of the major metabolic pathway resulting in GDP-L-fucose synthesis from GDP-D-mannose in procaryotic and eucaryotic cells [25].
• These results suggest that whereas UDP-glucose is translocated across the RER membrane in vitro, GDP-mannose is not transported [26].
• In the presence of GDP-mannose and/or UDP-galactose, membranes of R. leguminosarum first transferred mannose and then galactose to (Kdo)2-[4'-32P]-lipid IVA [27].
• These homologues also inhibited the transfer of N-acetylglucosamine-1-phosphate from UDP-N-acetylglucosamine to dolichyl phosphate in chick liver microsome preparations, whereas the transfer of mannose from GDP-mannose to the lipid acceptor was hardly affected [28].

Gene context of guanosine diphosphate mannose

• The VRG4 gene is required for GDP-mannose transport into the lumen of the Golgi in the yeast, Saccharomyces cerevisiae [29].
• Phosphomannose isomerase (PMI40) catalyzes the conversion between fructose 6-phosphate and mannose 6-phosphate and thus connects glycolysis, i.e. energy production and GDP-mannose biosynthesis or cell wall synthesis in Saccharomyces cerevisiae [30].
• The ALG1 gene product has been shown to catalyze the transfer of a mannosyl residue from GDP-mannose to the lipid-linked acceptor GlcNAc2, yielding Man beta 1-4GlcNAc2-lipid, in lysates from Escherichia coli transformants [31].
• Partially purified recombinant PimB protein from Escherichia coli or membranes from M. smegmatis overexpressing the pimB gene were used in cell-free assays to show that PimB catalyzes the formation of triacylphosphatidylinositol dimannoside from GDP-mannose and triacylphosphatidylinositol monomannoside [32].
• The increase in transport activity due to the YEA4 overexpression is specific for UDP-GlcNAc, but not for UDP-galactose and GDP-mannose [33].

Analytical, diagnostic and therapeutic context of guanosine diphosphate mannose

• Some five or six radioactive oligosaccharides were formed from either MPP or from GDP-mannose and these oligosaccharides had similar mobilities upon paper chromatography [34].
• Incubation of this fraction with a mannopentaose, Man beta 1-->2Man alpha 1-->(2Man alpha 1-->)(2)2Man (alpha beta Man5), in the presence of GDP-mannose followed by high performance liquid chromatography showed the formation of a mannohexaose [35].
• Ultraviolet absorption spectra, chromatographic behaviour, gas-liquid chromatography coupled to mass spectrometry analysis revealed that GDP-D-mannose had been converted into GDP-L-fucose [36].
• Incubation of membranes with detergents such as Brij 35 and Lubrol PX released soluble fractions that transferred the sugar from GDP-Mannose mostly into mannoproteins, which were separated by affinity chromatography on Concanavilin A-Sepharose 4B into lectin-reacting and non-reacting fractions [37].
• Reaction products from GDP-d-mannose, as produced by GME catalysis, were separated by recycling HPLC on an ODS column, and were determined to be GDP-l-galactose and GDP-l-gulose, based on their NMR spectra and sugar analysis [38].

References