Cross-Examining Cancer Drug—Enzyme Interactions

  • Author: Victoria Barton
  • Published Date: 29 June 2011
  • Source / Publisher: Chemistry - A European Journal/Wiley-VCH
  • Copyright: Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
thumbnail image: Cross-Examining Cancer Drug—Enzyme Interactions

Related Societies

The effectiveness of platinum-based cancer drugs are limited by drug resistance, which, in some cancers, is associated to over expression of a major detoxifying enzyme; the π class glutathione S-transferase (GST P1-1). Ethacraplatin (EA-CPT) was designed as a cancer drug that could also target the GST enzymes.



Michael Parker and co-workers, University of Melbourne, Australia, have combined X-ray crystallography and molecular modeling to visualize how EA-CPT is recognized by the dimeric GST P1-1 enzyme (protein backbone = pink ribbons) and why it is more potent than its individual components; ethacrynate acid (EA = orange spheres) and cisplatin.


EA-CPT was shown to preferentially dock at the dimer interface at GST P1-1. Subsequent interaction with the enzyme resulted in docking of EA at both active sites, whereas the Pt moiety remained bound at the dimer interface. The EA ligands dissociate from the metal-bound enzyme complex, where they likely diffuse through a surface cavity (grey surface) a short distance to the active sites of each monomer, to covalently bind and inhibit the enzyme.

Images: (c) Wiley-VCH


Article Views: 3747

Sign in Area

Please sign in below

Additional Sign In options

Please note that to comment on an article you must be registered and logged in.
Registration is for free, you may already be registered to receive, e.g., the newsletter. When you register on this website, please ensure you view our terms and conditions. All comments are subject to moderation.

Article Comments - To add a comment please sign in

If you would like to reuse any content, in print or online, from ChemistryViews.org, please contact us first for permission. more

Follow on Facebook Follow on Twitter Follow on LinkedIn Follow on Instagram RSS Sign up for newsletters

Magazine of Chemistry Europe (16 European Chemical Societies) published by Wiley-VCH