Binding of VIV O2+ , VIV OL, VIV OL2 and VV O2 L Moieties to Proteins: X-ray/Theoretical Characterization and Biological Implications

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 O²⁺ and V^IV OL²⁺ , where L=2,2'-bipyridine or 1,10-phenanthroline (phen), and of trypsin with V^IV O(picolinato)₂ and V^V O₂ (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 O₂ (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.

Keywords: X-ray diffraction; metalloproteins; molecular modeling; structure elucidation; vanadium.