Binding of V O , V OL, V OL and V O L Moieties to Proteins: X-ray/Theoretical Characterization and Biological Implications.

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 O and V OL , where L=2,2'-bipyridine or 1,10-phenanthroline (phen), and of trypsin with V O(picolinato) and V O (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 O (phen) and trypsin-V 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 and 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.