The ɛ-(γ-Glutamyl)Lysine Crosslink and the Catalytic Role of Transglutaminases

Abstract

The production of functional protein units in many cases requires the formation of covalent bonds, and prevalent among these are crosslinks within and between molecules that play a major role in maintaining gross forms of structure and limiting degrees of extensibility. This chapter describes the current knowledge of the distribution, formation, and function of the ɛ-(γ-glutamyl)lysine crosslink, and focuses largely on the crosslink known to be or believed to be formed by the catalytic action of transglutaminases. These enzymes catalyze a calcium-dependent acyl-transfer reaction in which the γ-carboxamide groups of peptide-bound glutamine residues are the acyl donors. Participation of ɛ-amino groups of peptide-bound lysine residues as acyl acceptors yields ɛ-(γ-glutamyl)lysine crosslinks. Although, there is a little doubt that the enzymes described in the chapter are capable of catalyzing crosslink formation, individualities of substrate preference notwithstanding, current data do not prove that this is the biological function of each. The chapter is believed to permit critical evaluation of the information available, suggest areas that hold the greatest opportunity for advances, and will, as a consequence, stimulate further investigations of the synthesis, distribution, and function of the ɛ-(γ-glutamyl)lysine crosslink.