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The resulting reaction mixture was left stirring for several hours.
In a further embodiment, the present invention is directed toward a modified TetR(Z) protein comprising an amino acid substitution at an amino acid position selected from the group consisting of positions 63, 74, 75, 95, 99, 100, 103, 104, 105, 107, 118, 137, 165, 166, 167, 181, 185, and 189 of the TetR(Z) protein as depicted in SEQ ID NO: 50, wherein said modified TetR(Z) protein binds a TetR(Z) operator sequence with greater affinity in the presence of tetracycline than in the absence of tetracycline, where: the amino acid substitution at position 63 is asparagine, the amino acid substitution at position 74 is valine; the amino acid substitution at position 75 is valine; the amino acid substitution at position 95 is glutamine; the amino acid substitution at position 99 is selected from the group consisting of glycine and glutamic acid; the amino acid substitution at position 99 is glycine; the amino acid substitution at position 99 is glutamic acid; the amino acid substitution at position 100 is arginine; the amino acid substitution at position 100 is glutamic acid; the amino acid substitution at position 103 is glutamic acid; the amino acid substitution at position 104 is alanine; the amino acid substitution at position 105 is histidine; the amino acid substitution at position 107 is serine; the amino acid substitution at position 118 is valine; the amino acid substitution at position 137 is selected from the group consisting of arginine, lysine, and histidine; the amino acid substitution at position 165 is cysteine; the amino acid substitution at position 166 is leucine; the amino acid substitution at position 167 is valine; the amino acid substitution at position 181 is glycine; the amino acid substitution at position 185 is tryptophan; and the amino acid substitution at position 189 is histidine? Rings that are joined through non-adjacent atoms are termed "bridged" rings!
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