Structurally, ubiquitin is an 8.5 kDa, 76 amino acid polypeptide that forms a compact structure with an exposed carboxy terminal tail containing a diglycine motif that can be covalently ligated via an isopeptide bond
to the primary e-amino group of lysine (Lys) residues on a target substrate.
Its insolubility is largely attributable to cross-linking of certain structural proteins by a series of transglutaminase (TGase) enzymes which form an [N.sup.[Epsilon]]([Gamma]-glutamyl) lysine isopeptide bond
between the [Gamma]-amide sidechain of a donor glutamine residue and the [Epsilon]-N[H.sub.2] sidechain group of an acceptor lysine residue.
FXIIIa is a transglutaminase that catalyzes the formation of isopeptide bonds
between the free amine group of a lysine residue and the acyl group at the end of the side chain of a glutamine residue .
He noted that aging slows ubiquitin-proteasome proteolytic activity, resulting in the accumulation of ubiquitinylated proteins via isopeptide bonds
. This accumulation causes the onset of inflammation.
As you may know, transglutaminase is a transferase that forms isopeptide bonds
between lysyl and glutaminyl residues.
It is possible that the EDTA-insensitive [[alpha].sub.2]M is covalently linked via transglutaminase-catalyzed isopeptide bonds
. The Limulus clot does contain such protein-protein bonds  and human [[alpha].sub.2]M is a substrate for transglutaminase crosslinking.
Thiol ester activation hydrolyses this bond, releasing the [gamma]-carbonyl of Gln, which in LAM establishes isopeptide bonds
with the [epsilon]-amino group of Lys-254 (3), and the thiol of Cys.