First crystal structure of an adduct formed upon reaction of a vanadium compound with human serum transferrin

The interaction of vanadium compounds of pharmaceutical interest with metal-transport proteins like human serum transferrin (hTF) is poorly understood. Direct structural evidence identifying vanadium binding sites on hTF is still lacking. Here, the X-ray structure of the adduct formed when the potential drug [V^IVO(acac)₂], with acac = acetylacetonato, reacts with human serum transferrin with Fe³⁺ bound at the C-lobe only (Fe_C-hTF) has been solved and compared with new structures of Fe_C-hTF used as controls. Structural analysis revealed the presence of a [V^V₂O₆]^2- anion that can be described as a divanadate(V) anion, [V^V₂O₇]^4-, that has one oxygen replaced by the phenolate oxygen of Tyr188. The two vanadium centers adopt tetrahedral geometry, consistent with V^V behavior. The binding does not alter the overall conformation of Fe_C-hTF that retains the open conformation of the N-lobe and the closed conformation of the C-lobe, remaining able to be recognized by the transferrin receptor.