Binding of V<sup>IV</sup>O<sup>2+</sup>, V<sup>IV</sup>OL, V<sup>IV</sup>OL<sub>2</sub> and V<sup>V</sup>O<sub>2</sub>L Moieties to Proteins: X‐ray/Theoretical Characterization and Biological Implications
Marino F. A. Santos, Giuseppe Sciortino, Isabel Correia, Andreia C. P. Fernandes, Teresa Santos‐Silva, Federico Pisanu, Eugenio Garribba, João Costa Pessoa
Abstract
Abstract Vanadium compounds have frequently been proposed as therapeutics, but their application has been hampered by the lack of information on the different V‐containing species that may form and how these interact with blood and cell proteins, and with enzymes. Herein, we report several resolved crystal structures of lysozyme with bound V IV O 2+ and V IV OL 2+ , where L=2,2’‐bipyridine or 1,10‐phenanthroline (phen), and of trypsin with V IV O(picolinato) 2 and V V O 2 (phen) + moieties. Computational studies complete the refinement and shed light on the relevant role of hydrophobic interactions, hydrogen bonds, and microsolvation in stabilizating the structure. Noteworthy is that the trypsin−V V O 2 (phen) and trypsin−V IV O(OH)(phen) adducts correspond to similar energies, thus suggesting a possible interconversion under physiological/biological conditions. The obtained data support the relevance of hydrolysis of V IV and V V complexes in the several types of binding established with proteins and the formation of different adducts that might contribute to their pharmacological action, and significantly widen our knowledge of vanadium–protein interactions.