Protein Posttranslational Modifications: The Chemistry of Proteome Diversifications

The diversity of distinct covalent forms of proteins (the proteome) greatly exceeds the number of proteins predicted by DNA coding capacities owing to directed posttranslational modifications. Enzymes dedicated to such protein modifications include 500 human protein kinases, 150 protein phosphatases, and 500 proteases. The major types of protein covalent modifications, such as phosphorylation, acetylation, glycosylation, methylation, and ubiquitylation, can be classified according to the type of amino acid side chain modified, the category of the modifying enzyme, and the extent of reversibility. Chemical events such as protein splicing, green fluorescent protein maturation, and proteasome autoactivations also represent posttranslational modifications. An understanding of the scope and pattern of the many posttranslational modifications in eukaryotic cells provides insight into the function and dynamics of proteome compositions. A variety of covalent alterations to the side chains and backbone atoms of proteins expand the diversity of proteomes beyond the number predicted by natural genome sequences. The predominant posttranslational modifications are described with an emphasis on the mechanisms of formation and reversal. The picture shows ADP ribosylation of a modified histidine residue of elongation factor eEF‐2 catalyed by diphtheria toxin.