Abstract:
:Deleting an important active-site residue of diphtheria toxin, glutamic acid-148, reduces the toxin's ADP-ribosyltransferase activity by a factor of greater than 10(4). We considered using this mutation to construct a recombinant toxoid for expression by live attenuated vaccines and explored second-site mutations that might cause reversion. Activity was partially restored by substituting glutamic acid for valine-147 or by extending the deletion by five residues toward the NH2 terminus, thereby placing glutamic acid-142 immediately adjacent to tyrosine-149. In both mutants the indicated glutamic acid may occupy a spatial locus similar to that of glutamic acid-148 in the unmutated protein. Simply deleting a crucial residue does not, therefore, provide confidence that a second-site mutation could not readily restore activity to a toxoid.
journal_name
Proc Natl Acad Sci U S Aauthors
Killeen KP,Escuyer V,Mekalanos JJ,Collier RJdoi
10.1073/pnas.89.13.6207keywords:
subject
Has Abstractpub_date
1992-07-01 00:00:00pages
6207-9issue
13eissn
0027-8424issn
1091-6490journal_volume
89pub_type
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