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, 12, 479-501

Zinc and the Zinc Proteome

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Zinc and the Zinc Proteome

Wolfgang Maret. Met Ions Life Sci.

Abstract

Zinc(II) ions are catalytic, structural, and regulatory cofactors in proteins. In contrast to painstakingly collecting the pieces by isolating and characterizing zinc proteins, 'omics' approaches are now allowing us to tease out information about zinc proteins from genomes and to piece together the information to a broader knowledge and appreciation of the role of zinc in biology. Estimates for the number of zinc proteins in the human genome and in genomes of other organisms have been derived from a bioinformatics approach: mining sequence databases for homologies of known zinc-coordination motifs with characteristic ligand signatures for metal binding and combining this information with the knowledge about metal-binding domains of proteins. This approach resulted in an impressive number of almost 3000 human zinc proteins and made major contributions to our understanding of the composition of the zinc proteome and the functions of zinc proteins. However, the impact of zinc on protein science is even greater. Predictions do not include yet undiscovered ligand signatures, coordination environments that employ complex binding patterns with nonsequential binding of ligands and ligand bridges, zinc/protein interactions at protein interfaces, and transient interactions of zinc(II) ions with proteins that are not known to be zinc proteins. All this information and recent discoveries of how cellular zinc is controlled and how zinc(II) ions function as signaling ions add an hitherto unrecognized dimension to the zinc proteome of multicellular eukaryotic organisms. Zinc proteomics employs a combination of approaches from different disciplines, such as bioinformatics, biology, inorganic biochemistry, and significantly, analytical and structural chemistry. It provides crucial large-scale datasets for interpreting the roles of zinc in health and disease at both a molecular and a global, systems biology, level.

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