Site-directed mutagenesis to fine-tune enzyme specificity

Abstract
We have used a combination of a genetic selection and oligonucleotide-directed mutagenesis to introduce a series of amino add replacements for a single residue into Escherichia coliglutaminyl-tRNA synthetase. The mutant enzymes mischarge supFtRNATyr, with glutamine, to varying degrees depending on the polarity of the side chain introduced but apparently not depending on the size or shape of the side chain. These results indicate that repulsive charge-charge interactions may be important for specific recognition of nucleic acids by proteins and illustrate how a mutant, derived from genetic selection, may be further modified in activity by oligonucleotide-directed mutagenesis.

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