Combining enzymatic and in silico studies to better understand polyoxometalates interactions with Ca2+-ATPase

Polyoxovanadates (POVs) are a subclass of polyoxometalates (POMs) that are well known for inhibiting several enzymes, such as Ca²⁺-ATPase. In this work, we investigated the interactions of pentadecavanadate (V₁₅Cl) and octadecavanadates (V₁₈I and V₁₈P) with sarcoplasmic reticulum Ca²⁺-ATPase using a combination of enzymatic assays, speciation studies and molecular modeling approaches. The Half-maximal inhibitory concentrations (IC₅₀) for V₁₈I and V₁₈P were approximately 5 uM, while for V₁₅Cl it was 14 uM. DFT calculation suggested a correlation between inhibitory activity and  the volume enclosed by the electrostatic isosurface for a series of POMs. Molecular docking of the POVs to Ca²⁺-ATPase in conformations E1 and E2 indicated that V₁₈I and V₁₅Cl preferentially bind to the phosphorylation  domain of the E1 conformation. Overall, it is suggested that POVs inhibitory potential depends on multiple factors that modulate non-covalent interactions with residues in the Ca²⁺-ATPase, pointing to a new understanding of POVs interactions with proteins