The 3 fundamental types of posttranslational modifications. The ribbon structure of a model protein is shown. The amino acid side chains and the peptide and disulfide bonds that bind the polypeptide backbone can be posttranslationally modified. Type 1 modifications are covalent additions of a molecule to an amino acid side chain. The side chains of 15 of the 20 common amino acids of proteins can be covalently modified in reactions that usually involve an enzyme and a cosubstrate.¹  The lysine and tyrosine side chains are shown. The most frequent Type 1 modification in humans is phosphorylation of tyrosine. Type 2 modifications are hydrolytic cleavage or isomerization of certain peptide bonds. Hydrolytic cleavage is catalyzed by proteases, which are tightly regulated in space and time because the cleavage is irreversible. Isomerization of the peptide bond on the C-terminal side of proline residues is catalyzed by peptidyl prolyl cis-trans isomerases. Type 3 modifications are reductive cleavage of certain disulfide bonds, known as allosteric disulfides. Allosteric disulfide bonds control the function of the mature protein in which they reside by mediating a change when they are cleaved by oxidoreductases or by thiol-disulfide exchange.