From Genes to Metalloproteins: A Bioinformatic Approach

Genome sequencing projects have provided researchers with detailed information on every gene present in a large variety of organisms. Each of these genes is responsible for producing one or more proteins (depending on processes such as alternative splicing and post-translational modification) that constitute the machineries needed to sustain cellular life. The ensemble of proteins that an organism is capable of producing is called the proteome. A significant share of each organism's proteome requires metal ions or metal-containing cofactors to carry out its physiological function (metalloproteome). Experimental methods for the characterization of the metalloproteome of even simple prokaryotic organisms are still not routinely available, therefore significant insights can currently be only obtained using bioinformatic approaches. Herein we review the results obtained from the bioinformatic analyses of a variety of organisms, including humans, in which the distribution of iron-, copper-, and zinc-binding proteins across the kingdoms of life were investigated. It was found that among the metals, zinc is required by the largest number of proteins in most organisms (on average, 10 % of the proteome in eukaryota is predicted to be zinc-binding), whereas copper is the least common. In addition, the majority of non-heme iron-binding proteins have homologs in each taxonomic domain (archaea, bacteria, eukaryota), whereas zinc- and copper-binding proteins are substantially differentiated in eukaryota with respect to prokaryotic organisms.