Interaction of Vanadium(IV) Species with Ubiquitin: A Combined Instrumental and Computational Approach

Valeria Ugone, Daniele Sanna, Giuseppe Sciortino, Jean Didier Maréchal, Eugenio Garribba

Research output: Contribution to journalArticleResearch

28 Citations (Scopus)


© 2019 American Chemical Society. The interaction of VIVO2+ ion and five VIVOL2 compounds with potential pharmacological application, where L indicates maltolate (ma), kojate (koj), acetylacetonate (acac), 1,2-dimethyl-3-hydroxy-4(1H)-pyridinonate (dhp), and l-mimosinate (mim), with ubiquitin (Ub) was studied by EPR, ESI-MS, and computational (docking and DFT) methods. The free metal ion VIVO2+ interacts with Glu, Asp, His, Thr, and Leu residues, but the most stable sites (named 1 and 2) involve the coordination of (Glu16, Glu18) and (Glu24, Asp52). In the system with VIVOL2 compounds, the type of binding depends on the vanadium concentration. When the concentration is in the mM range, the binding occurs with cis-VOL2(H2O), L = ma, koj, dhp, and mim, or with VO(acac)2: in the first case, the equatorial coordination of His68, Glu16, Glu18, or Asp21 residues yields species with formula n[VOL2]-Ub where n = 2-3, while with VO(acac)2 only noncovalent surface interactions are revealed. When the concentration of V is on the order of micromolar, the mono-chelated species VOL(H2O)2+ with L = ma, koj, acac, dhp, and mim, favored by the hydrolysis, interact with Ub, and adducts with composition n[VOL]-Ub (n = 1-2) are observed with the contemporaneous coordination of (Glu18, Asp21) or (Glu16, Glu18), and (Glu24, Asp52) or (Glu51, Asp52) donors. The results of this work suggest that the combined application of spectroscopic, spectrometric, and computational techniques allow the complete characterization of the ternary systems formed by a V compound and a model protein such as ubiquitin. The same approach can be applied, eventually changing the spectroscopic/spectrometric techniques, to study the interaction of other metal species with other proteins.
Original languageEnglish
Pages (from-to)8064-8078
Number of pages15
JournalInorganic Chemistry
Issue number12
Publication statusPublished - 17 Jun 2019


Dive into the research topics of 'Interaction of Vanadium(IV) Species with Ubiquitin: A Combined Instrumental and Computational Approach'. Together they form a unique fingerprint.

Cite this