The P-type ATPase inhibiting potential of polyoxotungstates.

Polyoxometalates (POMs) are transition metal complexes that exhibit a broad diversity of structures and properties rendering them promising for biological purposes. POMs are able to inhibit a series of biologically important enzymes, including phosphatases, and thus are able to affect many biochemical processes. In the present study, we analyzed and compared the inhibitory effects of nine different polyoxotungstates (POTs) on two P-type ATPases, Ca2+-ATPase from skeletal muscle and Na+/K+-ATPase from basal membrane of skin epithelia. For Ca2+-ATPase inhibition, an in vitro study was performed and the strongest inhibitors were determined to be the large heteropolytungstate K9(C2H8N)5[H10Se2W29O103] (Se2W29) and the Dawson-type POT K6[α-P2W18O62] (P2W18) exhibiting IC50 values of 0.3 and 0.6 μM, respectively. Promising results were also shown for the Keggin-based POTs K6H2[CoW11TiO40] (CoW11Ti, IC50 = 4 μM) and Na10[α-SiW9O34] (SiW9, IC50 = 16 μM), K14[As2W19O67(H2O)] (As2W19, IC50 = 28 μM) and the lacunary Dawson K12[α-H2P2W12O48] (P2W12, IC50 = 11 μM), whereas low inhibitory potencies were observed for the isopolytungstate Na12[H4W22O74] (W22, IC50 = 68 μM) and the Anderson-type Na6[TeW6O24] (TeW6, IC50 = 200 μM). Regarding the inhibition of Na+/K+-ATPase activity, for the first time an ex vivo study was conducted using the opercular epithelium of killifish in order to investigate the effects of POTs on the epithelial chloride secretion. Interestingly, 1 μM of the most potent Ca2+-ATPase inhibitor, Se2W29, showed only a minor inhibitory effect (14% inhibition) on Na+/K+-ATPase activity, whereas almost total inhibition (99% inhibition) was achieved using P2W18. The remaining POTs exhibited similar inhibition rates on both ATPases. These results reveal the high potential of some POTs to act as P-type ATPase inhibitors, with Se2W29 showing high selectivity towards Ca2+-ATPase.info:eu-repo/semantics/submittedVersio

Oxo-Replaced Polyoxometalates: There Is More than Oxygen

The presence of oxo-ligands is one of the main required characteristics for polyoxometalates (POMs), although some oxygen ions in a metallic environment can be replaced by other nonmetals, while maintaining the POM structure. The replacement of oxo-ligands offers a valuable approach to tune the charge distribution and connected properties like reducibility and hydrolytic stability of POMs for the development of tailored compounds. By assessing the reported catalytic and biological applications and connecting them to POM structures, the present review provides a guideline for synthetic approaches and aims to stimulate further applications where the oxo-replaced compounds are superior to their oxo-analogues. Oxo-replacement in POMs deserves more attention as a valuable tool to form chemically activated precursors for the synthesis of novel structures or to upgrade established structures with extraordinary properties for challenging applications

The crystallization additive hexatungstotellurate promotes the crystallization of the HSP70 nucleotide binding domain into two different crystal forms

<div><p>The use of the tellurium-centered Anderson−Evans polyoxotungstate [TeW₆O₂₄]⁶⁻ (TEW) as a crystallization additive has been described. Here, we present the use of TEW as an additive in the crystallization screening of the nucleotide binding domain (NBD) of HSP70. Crystallization screening of the HSP70 NBD in the absence of TEW using a standard commercial screen resulted in a single crystal form. An identical crystallization screen of the HSP70 NBD in the presence of TEW resulted in both the “TEW free” crystal form and an additional crystal form with a different crystal packing. TEW binding was observed in both crystal forms, either as a well-defined molecule or in overlapping alternate positions suggesting translational disorder. The structures were solved by both molecular replacement and single wavelength anomalous diffraction (SAD) using the anomalous signal of a single bound molecule of TEW. This study adds one more example of TEW binding to a protein and influencing its crystallization behavior.</p></div

Data collection and refinement statistics.

<p>Data collection and refinement statistics.</p

Surface potential of crystal form 2, site 1 calculated using APBS.

<p>Surface potential of crystal form 2, site 1 calculated using APBS.</p

Surface potential of crystal form 1 calculated using APBS.

<p>Surface potential of crystal form 1 calculated using APBS.</p

TEW bound to HSP70 at a crystal contact (crystal form 2, site 1).

<p>HSP70 is colored cyan, the symmetry related HSP70 is colored grey. The two alternate positions are shown with oxygen atoms colored red or yellow. 2Fo-Fc electron density (contoured at 2 σ) is shown for the TEW molecule.</p

Chemical structure of TEW.

<p>Chemical structure of TEW.</p

Surface potential of crystal form 2, site 2 calculated using APBS.

<p>Surface potential of crystal form 2, site 2 calculated using APBS.</p