4 years ago

Binding of Copper and Cisplatin to Atox1 Is Mediated by Glutathione through the Formation of Metal–Sulfur Clusters

Binding of Copper and Cisplatin to Atox1 Is Mediated by Glutathione through the Formation of Metal–Sulfur Clusters
Graham N. George, George A. Kaminski, Ingrid J. Pickering, Kelly L. Summers, Jerzy Bernholc, Julien J. H. Cotelesage, Kurt H. Nienaber, Miroslav Hodak, John P. Cvitkovic, Corey Yu, Natalia V. Dolgova, Oleg Y. Dmitriev
Copper is an essential nutrient required for many biological processes involved in primary metabolism, but free copper is toxic due to its ability to catalyze formation of free radicals. To prevent toxic effects, in the cell copper is bound to proteins and low molecular weight compounds, such as glutathione, at all times. The widely used chemotherapy agent cisplatin is known to bind to copper-transporting proteins, including copper chaperone Atox1. Cisplatin interactions with Atox1 and other copper transporters are linked to cancer resistance to platinum-based chemotherapy. Here we analyze the binding of copper and cisplatin to Atox1 in the presence of glutathione under redox conditions that mimic intracellular environment. We show that copper(I) and glutathione form large polymers with a molecular mass of approximately 8 kDa, which can transfer copper to Atox1. Cisplatin also can form polymers with glutathione, albeit at a slower rate. Analysis of simultaneous binding of copper and cisplatin to Atox1 under physiological conditions shows that both metals are bound to the protein through copper-sulfur-platinum bridges.

Publisher URL: http://dx.doi.org/10.1021/acs.biochem.7b00293

DOI: 10.1021/acs.biochem.7b00293

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.