LourenÃ§o, Gustavo J NÃ©ri, Iramaia A Sforni, Vitor C S Kameo, Rodolfo Lorand-Metze, Irene Lima, Carmen S P Polymorphisms of glutathione S-transferase Mu 1, glutathione S-transferase theta 1 and glutathione S-transferase Pi 1 genes in Hodgkin's lymphoma susceptibility and progression. This example demonstrates the functional plasticity of the glutathione transferase scaffold as well as the potential of rational active-site directed mutagenesis as a complement to DNA shuffling and other stochastic methods for the redesign of proteins with novel functions. The substrate selectivity of the mutated glutathione transferase was changed 7000-fold by five point mutations. Both the catalytic center activity (k(cat)) and catalytic efficiency (k(cat)/K(m)) match the values of the naturally evolved glutathione transferase A3-3, the most active steroid isomerase known in human tissues. However, the present work shows that the knowledge-based redesign restricted to substrate-binding residues in human glutathione transferase A2-2 can introduce high steroid double-bond isomerase activity into the enzyme originally characterized by glutathione peroxidase activity. Such attempts based on the comparison of similar structures with different substrate selectivities have previously met with limited success. For the engineering of enzymes with novel functions, it would be of great value if the necessary changes of the active site could be predicted and implemented. Successful attempts have frequently been based on directed molecular evolution involving libraries of random mutants in which variants with desired properties were identified. Pettersson, Par L Johansson, Ann-Sofie Mannervik, BengtĪ major goal in protein engineering is the tailor-making of enzymes for specified chemical reactions.

Transmutation of human glutathione transferase A2-2 with peroxidase activity into an efficient steroid isomerase.

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