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 (VO2+)-O-IV and (VOL2+)-O-IV, where L=2,2'-bipyridine or 1,10-phenanthroline (phen), and of trypsin with (VO)-O-IV(picolinato)(2) and (VO2)-O-V(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-(VO2)-O-V(phen) and trypsin-(VO)-O-IV(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.

Binding of VIV O2+ , VIV OL, VIV OL2 and VV O2 L Moieties to Proteins: X-ray/Theoretical Characterization and Biological Implications / Santos, Marino F A; Sciortino, Giuseppe; Correia, Isabel; Fernandes, Andreia C P; Santos-Silva, Teresa; Pisanu, Federico; Garribba, Eugenio; Costa Pessoa, João. - In: CHEMISTRY-A EUROPEAN JOURNAL. - ISSN 0947-6539. - 28:40(2022). [10.1002/chem.202200105]

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

Sciortino, Giuseppe;Pisanu, Federico;Garribba, Eugenio
;
2022

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 (VO2+)-O-IV and (VOL2+)-O-IV, where L=2,2'-bipyridine or 1,10-phenanthroline (phen), and of trypsin with (VO)-O-IV(picolinato)(2) and (VO2)-O-V(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-(VO2)-O-V(phen) and trypsin-(VO)-O-IV(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.
Binding of VIV O2+ , VIV OL, VIV OL2 and VV O2 L Moieties to Proteins: X-ray/Theoretical Characterization and Biological Implications / Santos, Marino F A; Sciortino, Giuseppe; Correia, Isabel; Fernandes, Andreia C P; Santos-Silva, Teresa; Pisanu, Federico; Garribba, Eugenio; Costa Pessoa, João. - In: CHEMISTRY-A EUROPEAN JOURNAL. - ISSN 0947-6539. - 28:40(2022). [10.1002/chem.202200105]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/297930
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