Department of Biochemistry and Organic Chemistry, Uppsala University, Biomedical Center, Box 576, SE-75123 Uppsala, Sweden.
J Biol Chem. 2010 Feb 19;285(8):5639-45. doi: 10.1074/jbc.M109.074757. Epub 2009 Dec 18.
Adaptive responses to novel toxic challenges provide selective advantages to organisms in evolution. Glutathione transferases (GSTs) play a pivotal role in the cellular defense because they are main contributors to the inactivation of genotoxic compounds of exogenous as well as of endogenous origins. GSTs are promiscuous enzymes catalyzing a variety of chemical reactions with numerous alternative substrates. Despite broad substrate acceptance, individual GSTs display pronounced selectivities such that only a limited number of substrates are transformed with high catalytic efficiency. The present study shows that minor structural changes in the C-terminal helix of mouse GST T1-1 induce major changes in the substrate-activity profile of the enzyme to favor novel chemical reactions and to suppress other reactions catalyzed by the parental enzyme.
对新的毒性挑战的适应反应为生物进化提供了选择性优势。谷胱甘肽转移酶（GSTs）在细胞防御中起着关键作用，因为它们是使外源性和内源性遗传毒性化合物失活的主要贡献者。GSTs 是一种具有多种化学活性的多功能酶，可以催化多种化学反应，具有许多替代底物。尽管具有广泛的底物接受能力，但个别 GSTs 显示出明显的选择性，使得只有有限数量的底物以高催化效率转化。本研究表明，小鼠 GST T1-1 的 C 端螺旋的微小结构变化会导致酶的底物-活性谱发生重大变化，有利于新的化学反应，并抑制亲本酶催化的其他反应。
