Comparison of high‐resolution structures of the diphtheria toxin repressor in complex with cobalt and zinc at the cation‐anion binding site

Publisher Website
Google Scholar
Abstract
The diphtheria toxin repressor (DtxR) from Coryne‐bacterium diphtheriae is a divalent‐metal activated repressor of chromosomal genes responsible for siderophore‐mediated iron‐uptake and of a gene on several corynebacteriophages that encodes diphtheria toxin. Even though DtxR is the best characterized iron‐dependent repressor to date, numerous key properties of the protein still remain to be explained. One is the role of the cation‐anion pair discovered in its first metal‐binding site. A second is the reason why zinc exhibits its activating effect only at a concentration 100‐fold higher than other divalent cations. In the presently reported 1.85 Å resolution Co‐DtxR structure at 100K, the sulfate anion in the cation‐anion‐binding site interacts with three side chains that are all conserved in the entire DtxR family, which points to a possible physiological role of the anion. A comparison of the 1.85 Å Cobalt‐DtxR structure at 100K and the 2.4 Å Zinc‐DtxR structure at room temperature revealed no significant differences. Hence, the difference in efficiency of Co2+ and Zn2+ to activate DtxR remains a mystery and might be hidden in the properties of the intriguing second metal‐binding site. Our studies do, however, provide a high resolution view of the cation‐anion‐binding site that has most likely evolved to interact not only with a cation but also with the anion in a very precise manner.

This publication has 26 references indexed in Scilit: