Transglutaminase

Transglutaminases are enzymes that in nature primarily catalyze the formation of an isopeptide bond between γ-carboxamide groups (-(C=O)NH2 ) of glutamine residue side chains and the ε-amino groups (-NH2 ) of lysine residue side chains with subsequent release of ammonia (NH3 ). Lysine and glutamine residues must be bound to a peptide or a protein so that this cross-linking (between separate molecules) or intramolecular (within the same molecule) reaction can happen. Bonds formed by transglutaminase exhibit high resistance to proteolytic degradation (proteolysis). The reaction is
Gln-(C=O)NH2 + NH2-Lys → Gln-(C=O)NH-Lys + NH3
Transglutaminases can also join a primary amine (RNH2 ) to the side chain carboxyamide group of a protein/peptide bound glutamine residue thus forming an isopeptide bond
Gln-(C=O)NH2 + RNH2 → Gln-(C=O)NHR + NH3
These enzymes can also deamidate glutamine residues to glutamic acid residues in the presence of water
Gln-(C=O)NH2 + H2O → Gln-COOH + NH3
Transglutaminase isolated from Streptomyces mobaraensis -bacteria for example, is a calcium-independent enzyme. Mammalian transglutaminases among other transglutaminases require Ca2+ ions as a cofactor.
Transglutaminases were first described in 1959. The exact biochemical activity of transglutaminases was discovered in blood coagulation protein factor XIII in 1968.
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. In the related condition dermatitis herpetiformis, in which small bowel changes are often found and which responds to dietary exclusion of gliadin-containing wheat products, epidermal transglutaminase is the predominant autoantigen.
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, and is used in a variety of processes, including the production of processed meat and fish products.
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
See also
Boneless Fish
Surimi
Bromelain
Papain
Ficain
References
Further reading
A transglutaminase catalyzing an acyl transfer reaction of a Γ-carboxyamide group of a glutamine residue in a peptide or protein chain in the absence of Ca2+
Food additives
Autoantigens
Calcium enzymes
Enzymes of known structure