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

谷胱甘肽S转移酶(GSTs)是一个多功能蛋白质大家族，在生物体抵御有毒化学物质的防御中起着至关重要的作用。然而，它们也攻击各种药物，因此是开发异构体特异性抑制剂的主要目标。我们将测定GSTs与一系列底物和抑制剂形成的络合物的三维原子结构，作为设计化合物以提高抗癌和其他药物疗效的基础。这是一个雄心勃勃、涉及面很广的项目，涉及世界各地的合作者。我们预计，这些结果不仅将极大地增加我们对一个重要酶家族的了解，而且还将在蛋白质折叠、催化、蛋白质工程、进化、药物设计和功能基因组学中得到应用。

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.