Preferred substrate structure of transglutaminases

Abstract

By catalytic reactions, transglutaminases (TGase) modify structure, functions and localizations of proteins. Identification of specific substrate proteins and analyses on the reaction products is the first step in clarifying the physiological significance of cross-linking and transamidation reactions. To date, in in vitro and in vivo analyses, a number of proteins have been identified as possible substrates by several methods. Additionally, each isozyme in the enzyme family has its specific preference for its recognition of the substrate proteins. During these investigations, structural properties and interaction with the enzyme appeared specific and the elegant mechanisms have been characterized. In the first part of this chapter, we will describe the basic knowledge regarding the mechanism of substrate enzyme reactions, substrates for major isozymes, and substrate sequences available for several experiments. In the second part of this chapter, our recent studies will be introduced, discussing identification of highly reactive substrate peptides on each isozyme from a random peptide library, applications for detection of activity, and identification of substrate candidates.