Structural studies of glutathione transferases: a model system for functional genomics and drug design

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Glutathione S-transferases (GSTs) are a large family of multi-functional proteins that play a vital role in an organism's defence against toxic chemicals. However, they also attack a variety of drugs and hence are a prime target for the development of isoform-specific inhibitors. We will determine the 3D atomic structures of GSTs in complex with a range of substrates and inhibitors as a basis for the design of compounds to improve the efficacy of anti-cancer and other drugs. This is an ambitious, wide-ranging project involving collaborators around the world. We expect the results will not only greatly increase our knowledge of an important enzyme family, but will also have applications in protein folding, catalysis, protein engineering, evolution, drug design and functional genomics.