Abstract
The object of this work was to test the hypothesis that failure to secrete the Z variant of human α1-antitrypsin is related to the loss of a particular structural feature, the Lys-290 to Glu-342 salt bridge. Oligonucleotide-directed mutagenesis was used to disrupt the salt bridge by substituting a glutamic acid for lysine at residue 290. RNA transcripts prepared from this mutant DNA and from the normal cDNA were both able to direct the synthesis of protein in a cell-free system and after injection into Xenopus oocytes. Furthermore, the constructed mutant α-antitrypsin was secreted as readily as the normal inhibitor.