Cadmium II Binding to Nucleic Acids

Despite the obvious toxic effects rai living cells, Cd is often used in in vitro studies as a probe of Mg or Ca (see Chapter 6) having the advantage of a higher affinity towards most hgands, including nucleotides and their cmistituents, as described in the previous sections. Below we consider now larger entities. 

The principle of cadmium(II) rescue experiments is as follows (see also refs [8,10]) Phosphorothioate nucleotides are inserted into a RNA at single, defined sites. In cases of significantly decreased or abolished enzymatic activity of the RNA and subsequent restoration of activity upon addition of soft metal ions like Cd , one assumes that the respective phosphate moiety coordinates a metal ion which is relevant for the catalytic activity of the ribozymes. 

The technique was first applied to the enzymes arginine kinase and creatinine kinase. Studies on ATPyS and on the stereospecificity for diastereomers of ATPotS 

More detailed information on cadmium(II) binding to nucleic acids is available from a small number of crystal structures of RNA as well as RNA- or DNA-protein 

The PDB structure of DNA polymerase p with 7 base pairs of DNA and ATP bound (PDB SICE) contains just one binding site in which DNA is involved. The cadmium(II) has contacts to four different amino acids and two phosphate oxygens it is also in coordination distance to 05 of adenine and 03 of a guanine. Additionally, four oxygen atoms of pyrophosphate coordinate the Cd . This is a good example of how DNA-Cd contacts can be facilitated by another main binding site. In this case, the pyrophosphate is required to bind a metal ion in this site as in its absence the site remains unoccupied [285]. 

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