Exploring the zinc proteome

Abstract

The advent of the complete sequences of several genomes offers unprecedented opportunities to identify all metalloproteins and to establish a comprehensive database for the role of essential metals in health and disease. This summary examines new aspects of zinc proteins, which are a major fraction of metalloproteins. Their coordination environments have typical spacings between the amino acids that provide the metal ligands. The recognition of such "signatures" spawned interest in searching sequence databases for possible zinc binding sites in other proteins, thus, in essence, performing genomic metal "analyses". In this manner, hundreds of catalytic zinc sites and thousands of structural zinc sites, many of which are generically referred to as zinc fingers, are predicted in the human proteome. However, dynamic zinc functions are not readily defined in these terms, suggesting that the number of zinc proteins (the zinc proteome) is significantly larger than the snapshot taken from currently known signatures. Protein interface sites, where zinc bridges proteins or their subunits, and inhibitory or regulatory sites, where zinc interacts with proteins transiently, are not all accounted for, nor are those for zinc in storage vesicles, transmembrane transporters, sensors, and proteins that participate in its cellular traffic. More structural work, experimental verification by analytical atomic spectroscopy, and speciation by hyphenated techniques, are needed before all signatures are defined and the complete zinc proteome can be functionally annotated. © The Royal Society of Chemistry 2004.