Binding Site of Corynebacterium Diphtheria Toxin and Metal Ion

Abstract

Diphtheria has been one of the most extensively studied bacterial infectious diseases of all time. These pivotal studies of the toxigenic bacterium Corynebacterius diphtheriae and its major virulence determinant (diphtheria toxin) have set the standard for other related bacterial protein toxin studies. The DtxR is a metal ion activated transcriptional regulator that is associated with the virulence of Corynebacteria diphtheriae. Structure determination indicates that there are 2 metal ion binding sites for each repressor monomer. Site directed mutagenesis indicates that binding site 2 (primary) is critical for recognition of target DNA repressor.

Using calorimetric methods, it has been shown that binding site 1 and 2 act independently of each other, and their role can be easily elucidated by conventional mutational assays. Diphtheria toxin and anthrax toxin research over the last 30 years has resulted in a comprehensive understanding of the structure function relationships of these toxins (for example, catalytic, transmbrane, and receptor binding domains) as well as identification of their Eukaryotic Cell Surface Receptors (ESRs), understanding of molecular events that lead to receptor-mediated intramuscularization of toxin into endosomal compartments, and pH-induced conformational changes necessary for the formation of pores in vesicle membranes. One of the most widely studied bacterial infectious diseases is diphtheria. In recent years, a great deal of research has been devoted to understanding in detail the molecular interactions of each of these toxins with eukaryotic cellular factors that play an important role in the rapid translocation of their catalytic domains through a pore on the trans-endosaic vesicle membrane and subsequent delivery into the cell cytochrome P450 system. These milestone studies of the toxin of toxigenic origin Corynebacterium diphtheriae and its main virulence determinant (diphtheria toxin) have set the standard for the study of related bacterial protein toxins.