Isopeptide bond

An isopeptide bond is an amide bond that is not present on the main chain of a protein. The bond forms between the carboxyl terminus of one protein and the amino group of a lysine residue on another (target) protein.

Isopeptide bonds can occur between the side chain amine of lysine and the side chain carboxyl groups of either glutamate or aspartate. Bond formation can be either enzyme catalyzed, as in the case for the bond formed between lysine and glutamine catalyzed by transglutaminases, or it can form spontaneously as observed in HK97 bacteriophage capsid formation and Gram-positive bacterial pili. Spontaneous isopeptide bond formation requires the presence of another residue, glutamic acid, which catalyzes bond formation in a proximity induced manner.