The bioorganic chemistry of transglutaminase — from mechanism to inhibition and engineering

Abstract

Through a multidisciplinary approach comprising organic synthesis, molecular biology, and physical organic kinetic studies, we have studied the mechanism of transglutaminase-mediated transamidation. More recently, we have applied our understanding of the mechanism to the design of reversible inhibitors and affinity labels for biological application. We have also undertaken the engineering of transglutaminase for its application as a “peptide synthase”. Herein, we present a brief overview of previously published work as well as recent results presented at the 2007 Merck–Frosst Centre for Therapeutic Research Award Lecture.Key words: transglutaminase, enzyme mechanism, enzyme inhibition, protein engineering