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

被引:38
作者
Keillor, Jeffrey W. [1 ]
Chica, Roberto A. [1 ]
Chabot, Nicolas [1 ]
Vinci, Vaierio [1 ]
Pardin, Christophe [1 ]
Fortin, Emanuelle [1 ]
Gillet, Steve M. F. G. [1 ]
Nakano, Yukiko [2 ]
Kaartinen, Mari T. [2 ]
Pelletier, Joelle N. [1 ]
Lubell, William D. [1 ]
机构
[1] Univ Montreal, Dept Chim, Montreal, PQ H3C 3J7, Canada
[2] McGill Univ, Fac Dent, Montreal, PQ H3A 2B2, Canada
关键词
transglutaminase; enzyme mechanism; enzyme inhibition; protein engineering;
D O I
10.1139/V08-024
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
收藏
页码:271 / 276
页数:6
相关论文
共 30 条
[1]  
AESCHLIMANN D, 1994, THROMB HAEMOSTASIS, V71, P402
[2]   Selection for improved subtiligases by phage display [J].
Atwell, S ;
Wells, JA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (17) :9497-9502
[3]   Kinetic characterization and identification of the acylation and glycosylation sites of recombinant human γ-glutamyltranspeptidase [J].
Castonguay, Roselyne ;
Halim, Dany ;
Morin, Mylene ;
Furtos, Alexandra ;
Lherbet, Christian ;
Bonneil, Eric ;
Thibault, Pierre ;
Keillor, Jeffrey W. .
BIOCHEMISTRY, 2007, 46 (43) :12253-12262
[4]   Tissue trans glutaminase acylation: Proposed role of conserved active site Tyr and Trp residues revealed by molecular modeling of peptide substrate binding [J].
Chica, RA ;
Gagnon, P ;
Keillor, JW ;
Pelletier, JN .
PROTEIN SCIENCE, 2004, 13 (04) :979-991
[5]  
Cooper AJL, 1997, J NEUROCHEM, V69, P431
[6]   Synthesis of dipeptide-bound epoxides and α,β-unsaturated amides as potential irreversible transglutaminase inhibitors [J].
de Macédo, P ;
Marrano, C ;
Keillor, JW .
BIOORGANIC & MEDICINAL CHEMISTRY, 2002, 10 (02) :355-360
[7]   Identification of tissue transglutaminase as the autoantigen of celiac disease [J].
Dieterich, W ;
Ehnis, T ;
Bauer, M ;
Donner, P ;
Volta, U ;
Riecken, EO ;
Schuppan, D .
NATURE MEDICINE, 1997, 3 (07) :797-801
[8]  
FOLK JE, 1969, J BIOL CHEM, V244, P3707
[9]  
Gerisch S, 1997, J PEPT SCI, V3, P93, DOI 10.1002/(SICI)1099-1387(199703)3:2<93::AID-PSC87>3.0.CO
[10]  
2-R