1. Glutathione S-transferases (GSTs) catalyze the conjugation of the reduced form of glutathione (GSH) to xenobiotic substrates for the purpose of detoxification at physiological pH 7.4. The reaction scheme and the structures of substrates are shown below. Which of the 20 amino acids would you predict most likely occur at the active site(s), and explain why? Figure 1: The reaction catalyzed by GST. Figure 2: The structure of GSH and the pKa values of the functional groups. 2. Suppose a mutant enzyme binds a substrate 100 times as tightly as does the native enzyme. What is the effect of this mutation on catalytic rate if the binding of the transition state is unaffected?
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