Disease relevance of dihydroxy-dioxo-tungsten

• Tungstate was orally administered to 7.5-week-old male Zucker diabetic fatty (ZDF) rats that already showed moderate hyperglycemia (180 +/- 16 mg/dl) [1].
• The X-ray crystal structures of Yersinia tyrosine phosphatase with bound tungstate and nitrate. Mechanistic implications [2].
• Tungstate Uptake by a highly specific ABC transporter in Eubacterium acidaminophilum [3].
• The genes encoding the tungstate-specific ABC transporter exhibited highest similarities to putative transporters from Methanobacterium thermoautotrophicum, Haloferax volcanii, Vibrio cholerae, and Campylobacter jejuni [3].
• The apo-nitrate reductase precursor in an Escherichia coli chlB mutant preparation obtained following growth in the presence of tungstate is activated by incubation with protein FA and a heat-treated preparation from an E. coli crude extract [4].

High impact information on dihydroxy-dioxo-tungsten

• Binding of tungstate triggers a conformational change that traps the oxyanion and swings Asp 356, an important catalytic residue, by approximately 6 A into the active site [5].
• We also demonstrate that the SurE protein exhibits a divalent metal ion-dependent phosphatase activity that is inhibited by vanadate or tungstate [6].
• A tungstate derivative used in the X-ray analysis is a competitive inhibitor and places the active site of fumarase in a region which includes atoms from three of the four subunits [7].
• These results show a direct involvement of ERK1/2 in the mechanism of action of tungstate at the hepatic level [8].
• In contrast, at low concentrations, tungstate induced a transient strong activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) after 5-10 min of treatment, in a similar way to insulin [8].

Chemical compound and disease context of dihydroxy-dioxo-tungsten

• The direct demonstration of the requirement for molybdenum cofactor in the E. coli tungstate-grown chlB complementation system is an important step towards the molecular definition of the activation process and an understanding of the mechanism of cofactor acquisition during molybdoenzyme biosynthesis [4].
• The inhibition constants for vanadate, chromate, molybdate, and tungstate have been determined with Escherichia coli alkaline phosphatase, potato acid phosphatase, and Helix pomatia aryl sulfatase [9].
• In contrast, tungstate only partially inhibited sulfonate reduction by both SRB and Desulfitobacterium spp [10].
• Importantly, even completely NR-free mutants, as well as cells grown on tungstate, emitted NO when fed with nitrite under anoxia [11].
• Influence of tungstate on the formation and activities of four reductases in Proteus mirabilis: identification of two new molybdo-enzymes: chlorate reductase and tetrathionate reductase [12].

Biological context of dihydroxy-dioxo-tungsten

• The crystal structures of the protein-tyrosine phosphatase SHP-1 catalytic domain and the complex it forms with the substrate analogue tungstate have been determined and refined to crystallographic R values of 0.209 at 2.5 A resolution and 0.207 at 2.8 A resolution, respectively [13].
• In islets from treated diabetic rats, tungstate is able to increase the phosphorylation state of PDX-1 through the activation of p38 [14].
• Tungstate decreases weight gain and adiposity in obese rats through increased thermogenesis and lipid oxidation [15].
• Multiple inhibition kinetics suggests that vanadate is mutually exclusive with molybdate, tungstate, and vanadyl cation [16].
• The inhibitors tungstate and vinyl sulfonate, which are known to bind to active site residues comprising the core domain, protected Lys53 from acetylation [17].

Anatomical context of dihydroxy-dioxo-tungsten

• In primary cultured hepatocytes, tungstate showed insulin-like actions, which led to an increase in glycogen synthesis and accumulation [8].
• Stable and functional regeneration of pancreatic beta-cell population in nSTZ-rats treated with tungstate [14].
• We examined the effects of tungstate administration in the beta-cell mass of the pancreas as well as its therapeutic potential [14].
• When the antiprogestin [3H]RU486 was used instead of [3H]R5020 as a ligand, a 9 S PR was also found in the cytosol, but a nonactivated "8.5 S" receptor complex was identified in the high salt nuclear fraction in presence of tungstate ions [18].
• Micrographs of isolated gap junction specimens, negatively stained with one molybdate, three tungstate and three uranyl stains, were recorded at low and high irradiation [19].

Associations of dihydroxy-dioxo-tungsten with other chemical compounds

• Among the various oxyanions tested, only tungstate replaced molybdate in the repression of modA by ModE, but the affinity of ModE-tungstate for modABCD operator DNA was 6 times lower than with ModE-molybdate [20].
• The genes tupABC coding for an ABC transporter specific for tungstate were cloned in the downstream region of genes encoding a tungsten-containing formate dehydrogenase [3].
• Transformation brought about at 0 degrees C by salt, ammonium sulfate precipitation, or gel filtration is also blocked by both molybdate and tungstate [21].
• Stabilization with tungstate and/or cross-linking permitted immunoaffinity purification of untransformed rabbit as well as calf PR and ER on EC1-Affi-Gel 10 column (an anti-p59 immunoadsorbant) [22].
• On the other hand, both molybdate and tungstate increase fructose 2,6-bisphosphate levels and counteract the decrease in this metabolite induced by glucagon [23].

Gene context of dihydroxy-dioxo-tungsten

• Experiments with a specific inhibitor of ERK1/2 activation and kinase assays indicate that these proteins were directly involved in the stimulation of glycogen synthase and glycogen synthesis induced by tungstate without a direct involvement of protein kinase B (PKB/Akt) [8].
• Herein, we report the 1.9 A X-ray crystal structures of a member of the third subclass, magnesium-dependent phosphatase-1 (MDP-1) both in its unliganded form and with the product analogue, tungstate, bound to the active site [24].
• The modEABC operon was also repressed by tungstate and to a lesser extent by vanadate. modE, the first gene in the modEABC operon, controlled the Mo-dependent transcription of both operons [25].
• Transition metal oxyanions, such as molybdate, tungstate and vandadate, have been shown to prevent in vitro hormone-induced activation of the glucocorticoid receptor (GR) by blocking dissociation of the GR/heat shock protein heterocomplex [26].
• The ability of the Chfr FHA domain to recognize tungstate suggests that it shares the ability with other FHA domains to bind phosphoproteins [27].

Analytical, diagnostic and therapeutic context of dihydroxy-dioxo-tungsten

• As observed for the tungstate-stabilized receptor, the cross-linked receptor dissociated neither on gradient containing 0.4 M KCl (9.5 +/- 0.1 S (n = 3] nor during HPLC performed in 0.4 M KCl (RS = 6.5 +/- 0.3 (n = 4] [28].
• Oral administration of tungstate for 15 days normalized glycaemia in these diabetic animals (4.6 vs 7.8 mmol/l) [29].
• Aortic occlusion was established in rabbits (standard or tungstate diet) for 40 min by 2 h reperfusion [30].
• One hundred patients underwent excretory urography and a comparison was made of ten-minute, well-collimated images that were obtained with both par-speed and rare-earth screens, the latter being 6.5 times faster than the par-speed calcium tungstate screens [31].
• Using isothermal titration calorimetry, WtpA was observed to bind tungstate (dissociation constant [K(D)] of 17 +/- 7 pM) and molybdate (K(D) of 11 +/- 5 nM) with a stoichiometry of 1.0 mol oxoanion per mole of protein [32].

References