Interactions between uranium(vi) and phosphopeptide: experimental and theoretical investigations

Uranium is an essential actinide element in nuclear fuel cycles, and protein phosphorylation is one type of most important post-translational modifications. It is of great interest to study the interactions between uranyl ions and phosphorylated proteins. In this study, a phosphorylated pentapeptide (WpTPpTW, P(1)) motif was designed as a model to mimic possible coordination sites in genuine phosphorylated proteins. Electrospray ionization mass spectrometry (ESI-MS) results suggested that uranyl-P(1) complexes with chemical stoichiometry of 1 : 1 and 1 : 2 were both available. The conditional stability constant of the 1 : 1 complex uranyl-P(1) was determined to be 6.6 ± 0.2 at pH 4.0 by tryptophan fluorescence titrations, which is almost three orders of magnitude higher than that of the complex of nonphosphorylated peptide. The results of extended X-ray absorption fine structure (EXAFS) combined with density functional theoretical calculations suggested that uranyl ions coordinated with one phosphoryl and carboxyl groups of P(1) in a mono-dentate fashion, and three water molecules. This study on the simple metal-peptide system could provide basic information for locating the uranyl coordination site in some important phosphorylated proteins which is useful for evaluating the chemical toxicity of uranyl in vivo.