From nucleotides to ribozymes—A comparison of their metal ion binding properties

Abstract

It is undisputable that the fates of metal ions and nucleic acids are inescapably interwoven. Metal ions are essential for charge compensation of the negatively charged phosphate–sugar backbone, they are instrumental for proper folding, and last but not least they are crucial cofactors for ribozyme catalysis. Considerable progress has been achieved in the past few years on the identification of metal ion binding sites in large DNA and RNA molecules, like in ribozymes including the ribosome. Hereby, most information was gained from crystallography, which fails to explain metal ion binding equilibria in solution as well as the factors that determine the coordination of a metal ion to a specific site. In contrast, such information is readily available for the low-molecular building blocks of large nucleic acids, i.e. for mononucleotides and to some extent also dinucleotides. In this review, we combine and compare for the first time both sets of information. The focus is thereby set on Mg 2+, Ca 2+, Mn 2+, and Cd 2+ because these four metal ions are either freely available in cells, have a large impact on the catalytic rate of ribozymes, and/or are often applied in RNA biochemistry. Our comparisons show that results obtained from small molecules can be directly transposed to the findings in large RNA structures like the ribosome. For example, the basic coordination-chemical properties of the different metal ions are reflected in their binding to large nucleic acid structures: macrochelate formation, e.g. the simultaneous intranucleotide coordination of a Mg 2+ ion to the phosphate unit and the N7 site of a purine nucleobase (be it inner- or outersphere), is well known for mononucleotides. We show that the frequency of occurrence of this type of coordination is the same for mononucleotides and the ribosome.