title: Actin as a potential target for decavanadate.
abstract: ATP prevents G-actin cysteine oxidation and vanadyl formation specifically induced by decavanadate, suggesting that the oxometalate-protein interaction is affected by the nucleotide. The ATP exchange rate is increased by 2-fold due to the presence of decavanadate when compared with control actin (3.1×10(-3) s(-1)), and an apparent dissociation constant (k(dapp)) of 227.4±25.7 μM and 112.3±8.7 μM was obtained in absence or presence of 20 μM V(10), respectively. Moreover, concentrations as low as 50 μM of decameric vanadate species (V(10)) increases the relative G-actin intrinsic fluorescence intensity by approximately 80% whereas for a 10-fold concentration of monomeric vanadate (V(1)) no effects were observed. Upon decavanadate titration, it was observed a linear increase in G-actin hydrophobic surface (2.6-fold), while no changes were detected for V(1) (0-200 μM). Taken together, three major ideas arise: i) ATP prevents decavanadate-induced G-actin cysteine oxidation and vanadate reduction; ii) decavanadate promotes actin conformational changes resulting on its inactivation, iii) decavanadate has an effect on actin ATP binding site. Once it is demonstrated that actin is a new potential target for decavanadate, being the ATP binding site a suitable site for decavanadate binding, it is proposed that some of the biological effects of vanadate can be, at least in part, explained by decavanadate interactions with actin.
authors.affiliation: DCBB-FCT and CCMar, University of Algarve, 8005-139 Faro, Portugal.
authors.forename: Susana
authors.initials: S
authors.lastname: Ramos
authors.forename: José J G
authors.initials: JJ
authors.lastname: Moura
authors.forename: Manuel
authors.initials: M
authors.lastname: Aureliano
mesh_terms: D000199:Actins / Q000737:chemistry*; D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D011817:Rabbits; D014638:Vanadates / Q000737:chemistry*
chemical_list: D000199:Actins; D014638:Vanadates; D000255:Adenosine Triphosphate