Multi-institutional collaboration yields important insight into titanium(IV) in the body and medicine
In a major breakthrough in the understanding of the role of titanium(IV) and its interaction mechanism with the human serum protein, transferrin-a group of researchers under the leadership of Prof. Arthur D. Tinoco from our Chemistry Department and the Department of Environmental Sciences recently reported their findings in the Journal of the American Chemical Society (DOI:10.1021/jacs.6b01966). This work was accomplished via a multi-institutional collaboration with Prof. Nicholas Noinaj at Purdue University and Timothy B. Parks, RN from the VA Caribbean Healthcare System in San Juan, PR. The 2016 article “Unusual Synergism of Transferrin and Citrate in the Regulation of Ti(IV) Speciation, Transport, and Toxicity,” is of immense importance as titanium is a very abundant element found in food additives, white pigment, and bone implants but the understanding about the ways it can interact with human proteins and impact human health on the molecular level is obscure. In an effort to better understand how titanium interacts with serum transferrin, the iron(III) transport protein in blood, graduate Environmental Sciences students Manoj Saxena and Shweta Sharma were instrumental in obtaining high quality crystals of the titanium(IV) bound transferrin. This step was crucial for the successful elucidation of the metal binding details at the atomic level by X-ray crystallography aided by Prof. Noinaj. In a series of ligand competitive binding studies and cell-based assays, Prof. Tinoco along with Shweta, Mr. Parks, the Postdoctoral research assistant Dr. Yamixa Delgado, Chemistry graduate student Sergio Armando Loza-Rosas, and former Chemistry undergraduate students Ernesto P. Quiñones González and Steven E. Conklin, further investigated the implications of this titanium(IV) binding on the protein stability/conformation and its ability to transport the metal into cells. A profound finding was the synergism of the small molecule citrate and transferrin in regulating the speciation of titanium(IV) and maintaining it as a nontoxic and potentially bioavailable species. These researchers are now on the quest to determine if the human body uses titanium(IV) for a vital function.
- The co-author Nicole Zambrana worked for two summers on this project for her ACS Project Seed Research program fellowship.
- This work provides new insight into the development of potent Ti(IV) anticancer drugs.
Top row: Prof. Tinoco and Manoj Saxena
Middle: Timothy B. Parks, Sergio A. Loza-Rosas, Nicole Zambrana
Bottom: Ernesto P. Quiñones González, Shweta Sharma, Dr. Yamixa Delgado