https://www.selleckchem.com/products/pyridostatin-trifluoroacetate-salt.html The covalent protein-ligand linkage enabled structural characterization of these trapped, off-pathway oligomers using X-ray crystallography and NMR, providing insight into why tetramer stabilization inhibits amyloid assembly. Our findings highlight the power of "post-translational chemical modification" as a tool to study biological molecular mechanisms.The experimental data collected over the past 15 years on the interaction of decavanadate(V) (V10O286-; V10), a polyoxometalate (POM) with promising anticancer and antibacterial action, with G-actin, were rationalized by using several computational approaches (docking, density functional theory (DFT), and molecular dynamics (MD)). Moreover, a comparison with the isostructural and more stable decaniobate(V) (Nb10O286-; Nb10) was carried out. Four binding sites were identified, named α, β, γ, and δ, the site α being the catalytic nucleotide site located in the cleft of the enzyme at the interface of the subdomains II and IV. It was observed that the site α is preferred by V10, whereas Nb10 is more stable at the site β; this indicates that, differently from other proteins, G-actin could contemporaneously bind the two POMs, whose action would be synergistic. Both decavanadate and decaniobate induce conformational rearrangements in G-actin, larger for V10 than Nb10. Moreover, the binding mode of oxidovanadium(IV) ion, VIVO2+, formed upon the reduction of decavanadate(V) by the -SH groups of accessible cysteine residues, is also found in the catalytic site α with (His161, Asp154) coordination; this adduct overlaps significantly with the region where ATP is bound, accounting for the competition between V10 and its reduction product VIVO2+ with ATP, as previously observed by EPR spectroscopy. Finally, the competition with ATP was rationalized since decavanadate prefers the nucleotide site α, Ca2+-ATP displaces V10 from this site, while the competiti