Vanadate

About: Vanadate is a research topic. Over the lifetime, 4497 publications have been published within this topic receiving 120109 citations. The topic is also known as: vanadate.

Crystal structure and functional analysis of the SurE protein identify a novel phosphatase family.

Abstract: Homologs of the Escherichia coli surE gene are present in many eubacteria and archaea. Despite the evolutionary conservation, little information is available on the structure and function of their gene products. We have determined the crystal structure of the SurE protein from Thermotoga maritima. The structure reveals the dimeric arrangement of the subunits and an active site around a bound metal ion. We also demonstrate that the SurE protein exhibits a divalent metal ion-dependent phosphatase activity that is inhibited by vanadate or tungstate. In the vanadate- and tungstate-complexed structures, the inhibitors bind adjacent to the divalent metal ion. Our structural and functional analyses identify the SurE proteins as a novel family of metal ion-dependent phosphatases.

Characterization of the ATPase activity of the Mr 170,000 to 180,000 membrane glycoprotein (P-glycoprotein) associated with multidrug resistance in K562/ADM cells.

Abstract: The Mr 170,000 to 180,000 membrane glycoprotein associated with multidrug resistance (P-glycoprotein) is involved in drug transport mechanisms across the plasma membrane of multidrug-resistant cells. We have recently reported the purification of P-glycoprotein. The purified P-glycoprotein was found to have an ATPase activity, which might be coupled with the active efflux of anticancer drugs. In the present study, we have further studied the properties of the P-glycoprotein ATPase activity by an immobilized enzyme assay procedure using a P-glycoprotein-antibody-Protein A-Sepharose complex. GTP was also hydrolyzed by the P-glycoprotein, although less efficiently than ATP. The ATPase activity of P-glycoprotein had an optimal pH range around neutrality (pH 6.5–7.4). The detergent concentration of 3-[(3-cholamidopropyl)dimethyl-ammonio]-1-propane sulfonate used for protein solubilization was essential for enzyme recovery. Maximum activity was obtained when 0.1–0.2% 3-[(3-cholamidopropyl)dimethyl-ammonio]-propane sulfonate was used, while higher concentrations markedly inhibited the ATPase activity. The ATPase activity was dependent on Mg2+; maximum activity was obtained at 2–10 mm. Manganese and cobalt could substitute for magnesium as ionic cofactors. Divalent cations such as Ca2+, Zn2+, Ni2+, Cd2+, and Cu2+ inhibited the Mg2+-catalyzed ATP hydrolysis. N-Ethylmaleimide and vanadate inhibited the ATPase activity, while sodium azide or ouabain had no effect. Anticancer agents such as vincristine and Adriamycin did not affect the enzyme activity. In contrast, verapamil and trifluoperazine, agents which inhibit active drug efflux and restore drug sensitivity in resistant cells, caused an increase in the P-glycoprotein ATPase activity suggesting that P-glycoprotein might be the target molecule of these agents.

The potentiality of vanadium in medicinal applications.

Abstract: In the early treatment of diabetes with vanadium, inorganic vanadium compounds have been the focus of attention; organic vanadium compounds are nowadays increasingly attracting attention. A key compound is bis(maltolato)oxidovanadium, which became introduced into clinical tests Phase IIa. Organic ligands help modulate the bioavailability, transport and targeting mechanism of a vanadium compound. Commonly, however, the active onsite species is vanadyl (VO(2+)) or vanadate (H(2)VO(4) (-)), generated by biospeciation. The mode of operation can be ascribed to interaction of vanadate with phosphatases and kinases, and to modulation of the level of reactive oxygen species interfering with phosphatases and/or DNA. This operating mode has also been inferred for most cancerostatic vanadium compounds, although some, for example vanadocenes, may directly intercalate with DNA. Novel medicinal potentiality of vanadium compounds is geared towards endemic diseases in tropical countries, in particular leishmaniasis, Chagas' disease and amoebiasis, and viral infections such as Dengue fever, SARS and HIV.