Unusual Synergism of Transferrin and Citrate in the Regulation of Ti(IV) Speciation, Transport, and Toxicity

• DOI: 10.1021/jacs.6b01966
• Publication Date: 2016-04-12T22:00:07Z
• Authors: Arthur D. Tinoco; Manoj Saxena; Shweta Sharma; Nicholas Noinaj; Yamixa Delgado; Ernesto P. Quiñon...; Steven E. Conklin; Nicole Zambrana; Sergio A. Loza-Rosas; Timothy B. Parks
• Keywords: Genetic algorithm

Human serum transferrin (sTf) is a protein that mediates the transport of iron from blood to cells. Assisted by synergistic anion carbonate, sTf transports Fe(III) binding metal ion in closed conformation. Previous studies suggest sTf's role as potential transporter other metals such titanium. Ti widely used colorants, foods, and implants. A substantial amount leached into these However, fate its cells not known. Understanding interaction with assumes greater significance our ever increasing exposure form On basis vitro studies, it was speculated can bind Ti(IV) assisted anion. identity anion(s) conformational state which binds are Here we have solved first X-ray crystal structure Ti(IV)-bound sTf. We find an open conformation both carbonate citrate anions at sites, unprecedented for citrate. Studies cell lines Ti(IV)-sTf transported regulate metal's speciation attenuate cytotoxic property. Our results provide glimpse citrate-transferrin synergism regulation bioactivity offers insight future design Ti(IV)-based anticancer drugs.