Abstract
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.
Highlights
Cancer Society. □S The on-line version of this article contains supplemental Tables S1 and S2. 1 To whom correspondence should be addressed
To test if the reverse mutation, Arg to Trp, in a homologous enzyme is sufficient to suppress catalytic activities, this substitution was introduced in mouse GST T1-1
Met232 was mutated into Ala in both the wild type mouse GST T1-1 and the mutant R234W
Summary
Cancer Society. □S The on-line version of this article (available at http://www.jbc.org) contains supplemental Tables S1 and S2. 1 To whom correspondence should be addressed.
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