Transglutaminase

Examples

Nine transglutaminases have been characterised in humans, eight of which catalyse transamidation reactions. These TGases have a three or four-domain organization, with immunoglobulin-like domains surrounding the central catalytic domain. The core domain belongs to the papain-like protease superfamily (CA clan) and uses a Cys-His-Asp catalytic triad. Protein 4.2, also referred to as band 4.2, is a catalytically inactive member of the human transglutaminase family that has a Cys to Ala substitution at the catalytic triad.

Bacterial transglutaminases are single-domain proteins with a similarly-folded core. The transglutaminase found in some bacteria runs on a Cys-Asp diad.

Biological role

Transglutaminases form extensively cross-linked, generally insoluble protein polymers. These biological polymers are indispensable for an organism to create barriers and stable structures. Examples are blood clots (coagulation factor XIII), skin, and hair. The catalytic reaction is generally viewed as being irreversible, and must be closely monitored through extensive control mechanisms.

Role in disease

Deficiency of factor XIII (a rare genetic condition) predisposes to hemorrhage; concentrated enzyme can be used to correct the abnormality and reduce bleeding risk.

Anti-transglutaminase antibodies are found in celiac disease and may play a role in the small bowel damage in response to dietary gliadin that characterises this condition.

Recent research indicates that sufferers from neurological diseases like Huntington's and Parkinson's may have unusually high levels of one type of transglutaminase, tissue transglutaminase. It is hypothesized that tissue transglutaminase may be involved in the formation of the protein aggregates that causes Huntington's disease, although it is most likely not required.

Mutations in keratinocyte transglutaminase are implicated in lamellar ichthyosis.

Structural studies

As of late 2007, 19 structures have been solved for this class of enzymes, with PDB accession codes , , , , , , , , , , , , , , , , , , and .

Industrial and culinary applications

In commercial food processing, transglutaminase is used to bond proteins together. Examples of foods made using transglutaminase include imitation crabmeat, and fish balls. It is produced by Streptomyces mobaraensis fermentation in commercial quantities () or extracted from animal blood,{{cite news |last=Köhler |first=Wim |name-list-style=vanc |title=Gelijmde slavink |language=nl |publisher=NRC Handelsblad |date=2008-08-22 |df=dmy-all |url=https://www.nrc.nl/nieuws/2008/08/16/gelijmde-slavink-11589851-a1086306 |access-date=2024-07-06 |url-status=live |archive-url=https://web.archive.org/web/20090220132207/http://www.nrc.nl/achtergrond/article1960242.ece/Gelijmde_slavink |archive-date=20 February 2009

Transglutaminase can be used as a binding agent to improve the texture of protein-rich foods such as surimi or ham.

Thrombin–fibrinogen "meat glue" from bovine and porcine sources was banned throughout the European Union as a food additive in 2010. Transglutaminase remains allowed and is not required to be declared, as it is considered a processing aid and not an additive which remains present in the final product.

Molecular gastronomy

Transglutaminase is also used in molecular gastronomy to meld new textures with existing tastes. Besides these mainstream uses, transglutaminase has been used to create some unusual foods. British chef Heston Blumenthal is credited with the introduction of transglutaminase into modern cooking.

Wylie Dufresne, chef of New York's avant-garde restaurant wd~50, was introduced to transglutaminase by Blumenthal, and invented a "pasta" made from over 95% shrimp thanks to transglutaminase.

Synonyms

• protein-glutamine gamma-glutamyltransferase (systematic)
• fibrinoligase
• glutaminylpeptide gamma-glutamyltransferase
• protein-glutamine:amine gamma-glutamyltransferase
• R-glutaminyl-peptide:amine gamma-glutamyl transferase

References

References

1. (2002). "Transglutaminase Catalyzed Reactions: Impact on Food Applications". Journal of Food Science.
2. (1959). "The incorporation of amines into proteins". Arch Biochem Biophys.
3. (May 1968). "[Cross-link in fibrin polymerized by factor 13: epsilon-(gamma-glutamyl)lysine]". Science.
4. (August 2001). "Evolution of transglutaminase genes: identification of a transglutaminase gene cluster on human chromosome 15q15. Structure of the gene encoding transglutaminase X and a novel gene family member, transglutaminase Z". The Journal of Biological Chemistry.
5. (December 2002). "Transglutaminases: nature's biological glues". The Biochemical Journal.
6. (April 2014). "Transglutaminase regulation of cell function". Physiological Reviews.
7. (February 1998). "Isolation of a cDNA encoding a novel member of the transglutaminase gene family from human keratinocytes. Detection and identification of transglutaminase gene products based on reverse transcription-polymerase chain reaction with degenerate primers". The Journal of Biological Chemistry.
8. (November 2002). "Crystal structure of microbial transglutaminase from Streptoverticillium mobaraense". The Journal of Biological Chemistry.
9. (March 2002). "Epidermal transglutaminase (TGase 3) is the autoantigen of dermatitis herpetiformis". The Journal of Experimental Medicine.
10. (January 2002). "Evidence for a role for transglutaminase in Huntington's disease and the potential therapeutic implications". Neurochemistry International.
11. (May 2004). "Properties and applications of microbial transglutaminase". Applied Microbiology and Biotechnology.
12. (24 May 2010). "EU Bans 'Meat Glue' - Food Safety News".
13. Jon, Bonné. (2005-02-11). "Noodles, reinvented". NBC News.