Transglutaminases form isodipeptide crosslinks between acceptor amide groups of glutaminyl residues and donor epsilon-NH2 groups of lysines. In the epidermis, and other stratified squamous epithelial tissues, these enzymes are thought to be involved in the crosslinking of putative protein components to form the insoluble cell envelope. Using molecular biology approaches, we have found that there are 3 different transglutaminase activities in normal human and mouse epidermis. These are known as the K, C and E enzymes. Work is in progress to isolate and characterize clones encoding each of these and to determine the likely functions of these different activities in normal and abnormally keratinizing epidermis.

Project Start
Project End
Budget Start
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Support Year
1
Fiscal Year
1990
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National Institute of Arthritis and Musculoskeletal and Skin Diseases
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United States
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Ahvazi, Bijan; Boeshans, Karen M; Steinert, Peter M (2004) Crystal structure of transglutaminase 3 in complex with GMP: structural basis for nucleotide specificity. J Biol Chem 279:26716-25
Ahvazi, Bijan; Boeshans, Karen M; Idler, William et al. (2004) Structural basis for the coordinated regulation of transglutaminase 3 by guanine nucleotides and calcium/magnesium. J Biol Chem 279:7180-92
Kon, Atsushi; Takeda, Hitoshi; Sasaki, Hideyuki et al. (2003) Novel transglutaminase 1 gene mutations (R348X/Y365D) in a Japanese family with lamellar ichthyosis. J Invest Dermatol 120:170-2
Raghunath, Michael; Hennies, Hans-Christian; Ahvazi, Bijan et al. (2003) Self-healing collodion baby: a dynamic phenotype explained by a particular transglutaminase-1 mutation. J Invest Dermatol 120:224-8
Ahvazi, Bijan; Steinert, Peter M (2003) A model for the reaction mechanism of the transglutaminase 3 enzyme. Exp Mol Med 35:228-42
Kim, Soo-Youl; Jeong, Eun-Joo; Steinert, Peter M (2002) IFN-gamma induces transglutaminase 2 expression in rat small intestinal cells. J Interferon Cytokine Res 22:677-82
Ahvazi, Bijan; Kim, Hee Chul; Kee, Sun-Ho et al. (2002) Three-dimensional structure of the human transglutaminase 3 enzyme: binding of calcium ions changes structure for activation. EMBO J 21:2055-67
Kim, Soo Youl; Jeitner, Thomas M; Steinert, Peter M (2002) Transglutaminases in disease. Neurochem Int 40:85-103
Steinert, P M; Candi, E; Tarcsa, E et al. (1999) Transglutaminase crosslinking and structural studies of the human small proline rich 3 protein. Cell Death Differ 6:916-30
Candi, E; Tarcsa, E; Idler, W W et al. (1999) Transglutaminase cross-linking properties of the small proline-rich 1 family of cornified cell envelope proteins. Integration with loricrin. J Biol Chem 274:7226-37

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