STRUCTURE/FUNCTION RELATIONSHIPS OF DIPHTHERIA TOXIN A CHAIN

白喉毒素(DT)是一种典型的A-B类毒素。毒素的A链 含有酶活性(ADP-核糖基转移酶)。DT是 变种，试图单独灭活其中一个受体 对毒素的结合或酶活性。内部的两个替换 白喉毒素A链(H21G和G79D)被发现大大减少 毒素的酶活性似乎不会改变 毒素的整体构象。这两个DTA替换是 与野生型B链或已知的B链突变体结合 减少8000个装订。具有单一或多个突变的毒素 在大肠杆菌中进行了表达。其中几个突变株产生了一种 中和免疫反应相当于或好于 市面上可买到的化学毒素白喉疫苗。

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.