STRUCTURE/FUNCTION RELATIONSHIPS OF DIPHTHERIA TOXIN A CHAIN

白喉毒素是一种典型的a - b毒素。毒素的A链

Diphtheria toxin (DT) is a classic A-B toxin. The A chain of the toxin contains the enzymatic activity (ADP-ribosyltransferase). DT was mutangenized in an attempt to individually inactivate either the receptor binding or enzymatic activities to the toxin. Two substitutions within the diphtheria toxin A chain (H21G and G79D) were found to greatly reduce the enzymatic activity of the toxin yet did not appear to alter the overall conformation of the toxin. These two DTA substitutions were combined with either wild type B-chain or a B-chain mutant known to an 8000 reduction in binding. Toxins having single or multiple mutations were expressed in E. coli. Several of these mutants produce a neutralizing immune response that is equivalent to or better than commercially available chemically toxoided diphtheria vaccine.