Transglutaminase
| Transglutaminase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Transglutaminase example: coagulation factor XIII from human blood. PDB code: 1EVU. | |||||||||
| Identifiers | |||||||||
| EC no. | 2.3.2.13 | ||||||||
| CAS no. | 80146-85-6 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDBstructures | RCSB PDBPDBePDBsum | ||||||||
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Transglutaminasesareenzymesthat in nature primarilycatalyzethe formation of anisopeptide bondbetween γ-carboxamidegroups ( -(C=O)NH2) ofglutamineresidueside chainsand the ε-amino groups( -NH2) oflysineresidue side chains with subsequent release ofammonia( NH3). Lysine and glutamine residues must be bound to apeptideor aproteinso that thiscross-linking(between separate molecules) or intramolecular (within the same molecule) reaction can happen.[1]Bonds formed by transglutaminase exhibit high resistance to proteolytic degradation (proteolysis).[2]The reaction is[1]
- Gln-(C=O)NH2+NH2-Lys→ Gln-(C=O)NH-Lys + NH3
Transglutaminases can also join aprimary amine( RNH2) to the side chain carboxyamide group of a protein/peptide bound glutamine residue thus forming an isopeptide bond[1]
- Gln-(C=O)NH2+ RNH2→ Gln-(C=O)NHR + NH3
These enzymes can alsodeamidateglutamine residues toglutamic acidresidues in the presence of water[1]
- Gln-(C=O)NH2+ H2O →Gln-COOH+ NH3
Transglutaminase isolated fromStreptomyces mobaraensis-bacteriafor example, is acalcium-independent enzyme.Mammaliantransglutaminases among other transglutaminases require Ca2+ions as acofactor.[1]
Transglutaminases were first described in 1959.[3]The exact biochemical activity of transglutaminases was discovered inblood coagulationproteinfactor XIIIin 1968.[4]
Examples[edit]
Nine transglutaminases have been characterised in humans,[5]eight of which catalysetransamidationreactions. These TGases have a three or four-domain organization, withimmunoglobulin-like domains surrounding the central catalytic domain. The core domain belongs to thepapain-like proteasesuperfamily (CA clan) and uses a Cys-His-Aspcatalytic triad.[2]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.[6]
| Name | Gene | Activity | Chromosome | OMIM |
|---|---|---|---|---|
| Factor XIII(fibrin-stabilizing factor) chain A | F13A1 | coagulation | 6p25-p24 | 134570 |
| Keratinocyte transglutaminase | TGM1 | skin | 14q11.2 | 190195 |
| Tissue transglutaminase | TGM2 | ubiquitous | 20q11.2-q12 | 190196 |
| Epidermal transglutaminase | TGM3 | skin | 20q12 | 600238 |
| Prostate transglutaminase | TGM4 | prostate | 3p22-p21.33 | 600585 |
| TGM X | TGM5[7] | skin | 15q15.2 | 603805 |
| TGM Y | TGM6 | nerves, CNS | 20q11-15 | 613900 |
| TGM Z | TGM7 | testis, lung | 15q15.2 | 606776 |
| Protein 4.2 | EPB42 | erythrocytes, bone marrow, spleen | 15q15.2 | 177070 |
Bacterial transglutaminases are single-domain proteins with a similarly-folded core. The transglutaminase found in some bacteria runs on a Cys-Asp diad.[8]
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Biological role[edit]
Transglutaminases form extensively cross-linked, generally insoluble protein polymers. These biological polymers are indispensable for an organism to create barriers and stable structures. Examples areblood clots(coagulationfactor XIII),skin,andhair.The catalytic reaction is generally viewed as being irreversible, and must be closely monitored through extensive control mechanisms.[2]
Role in disease[edit]
Deficiency of factor XIII (a rare genetic condition) predisposes tohemorrhage;concentrated enzyme can be used to correct the abnormality and reduce bleeding risk.[2]
Anti-transglutaminase antibodiesare found inceliac diseaseand may play a role in thesmall boweldamage in response to dietarygliadinthat characterises this condition.[2]In the related conditiondermatitis 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.[9]
Recent research indicates that sufferers from neurological diseases likeHuntington's[10]andParkinson's[11]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.[2][12]
Mutations inkeratinocyte transglutaminaseare implicated inlamellar ichthyosis.
Structural studies[edit]
As of late 2007, 19structureshave been solved for this class of enzymes, withPDBaccession codes1EVU,1EX0,1F13,1FIE,1G0D,1GGT,1GGU,1GGY,1IU4,1KV3,1L9M,1L9N,1NUD,1NUF,1NUG,1QRK,1RLE,1SGX,and1VJJ.
Industrial and culinary applications[edit]
In commercial food processing, transglutaminase is used to bondproteinstogether. Examples of foods made using transglutaminase includeimitation crabmeat,andfish balls.It is produced byStreptomyces mobaraensisfermentationin commercial quantities (P81453) or extracted from animal blood,[13]and is used in a variety of processes, including the production of processedmeatandfishproducts.
Transglutaminase can be used as a binding agent to improve the texture of protein-rich foods such assurimiorham.[14]
Thrombin–fibrinogen"meat glue" from bovine and porcine sources was banned throughout the European Union as a food additive in 2010.[15]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[edit]
Transglutaminase is also used inmolecular gastronomyto meld new textures with existing tastes. Besides these mainstream uses, transglutaminase has been used to create some unusual foods. British chefHeston Blumenthalis credited with the introduction of transglutaminase into modern cooking.
Wylie Dufresne,chefof New York'savant-garderestaurantwd~50,was introduced to transglutaminase by Blumenthal, and invented a "pasta"made from over 95%shrimpthanks to transglutaminase.[16]
Synonyms[edit]
- protein-glutamine gamma-glutamyltransferase (systematic)
- fibrinoligase
- glutaminylpeptide gamma-glutamyltransferase
- protein-glutamine:amine gamma-glutamyltransferase
- R-glutaminyl-peptide:amine gamma-glutamyl transferase
See also[edit]
References[edit]
- ^abcdeDeJong GA, Koppelman SJ (2002). "Transglutaminase Catalyzed Reactions: Impact on Food Applications".Journal of Food Science.67(8): 2798–2806.doi:10.1111/j.1365-2621.2002.tb08819.x.
- ^abcdefGriffin M, Casadio R, Bergamini CM (December 2002)."Transglutaminases: nature's biological glues".The Biochemical Journal.368(Pt 2): 377–96.doi:10.1042/BJ20021234.PMC1223021.PMID12366374.
- ^Clarke DD, Mycek MJ, Neidle A, Waelsch H (1959). "The incorporation of amines into proteins".Arch Biochem Biophys.79:338–354.doi:10.1016/0003-9861(59)90413-8.
- ^Pisano JJ, Finlayson JS, Peyton MP (May 1968). "[Cross-link in fibrin polymerized by factor 13: epsilon-(gamma-glutamyl)lysine]".Science.160(3830): 892–3.Bibcode:1968Sci...160..892P.doi:10.1126/science.160.3830.892.PMID4967475.S2CID95459438.
- ^Grenard P, Bates MK, Aeschlimann D (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.276(35): 33066–78.doi:10.1074/jbc.M102553200.PMID11390390.
- ^Eckert RL, Kaartinen MT, Nurminskaya M, Belkin AM, Colak G, Johnson GV, Mehta K (April 2014)."Transglutaminase regulation of cell function".Physiological Reviews.94(2): 383–417.doi:10.1152/physrev.00019.2013.PMC4044299.PMID24692352.
- ^Aeschlimann D, Koeller MK, Allen-Hoffmann BL, Mosher DF (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.273(6): 3452–60.doi:10.1074/jbc.273.6.3452.PMID9452468.
- ^Kashiwagi T, Yokoyama K, Ishikawa K, Ono K, Ejima D, Matsui H, Suzuki E (November 2002)."Crystal structure of microbial transglutaminase from Streptoverticillium mobaraense".The Journal of Biological Chemistry.277(46): 44252–60.doi:10.1074/jbc.M203933200.PMID12221081.
- ^Sárdy M, Kárpáti S, Merkl B, Paulsson M, Smyth N (March 2002)."Epidermal transglutaminase (TGase 3) is the autoantigen of dermatitis herpetiformis".The Journal of Experimental Medicine.195(6): 747–57.doi:10.1084/jem.20011299.PMC2193738.PMID11901200.
- ^Karpuj MV, Becher MW, Steinman L (January 2002). "Evidence for a role for transglutaminase in Huntington's disease and the potential therapeutic implications".Neurochemistry International.40(1): 31–6.doi:10.1016/S0197-0186(01)00060-2.PMID11738470.S2CID40198925.
- ^Vermes I, Steur EN, Jirikowski GF, Haanen C (October 2004)."Elevated concentration of cerebrospinal fluid tissue transglutaminase in Parkinson's disease indicating apoptosis".Movement Disorders.19(10): 1252–4.doi:10.1002/mds.20197.PMID15368613.S2CID102503.
- ^Lesort M, Chun W, Tucholski J, Johnson GV (January 2002). "Does tissue transglutaminase play a role in Huntington's disease?".Neurochemistry International.40(1): 37–52.doi:10.1016/S0197-0186(01)00059-6.PMID11738471.S2CID7983848.
- ^Köhler W (22 August 2008)."Gelijmde slavink"(in Dutch).NRC Handelsblad.Archivedfrom the original on 20 February 2009.Retrieved6 July2024.
- ^Yokoyama K, Nio N, Kikuchi Y (May 2004). "Properties and applications of microbial transglutaminase".Applied Microbiology and Biotechnology.64(4): 447–54.doi:10.1007/s00253-003-1539-5.PMID14740191.S2CID19068193.
- ^"EU Bans 'Meat Glue' - Food Safety News".foodsafetynews.24 May 2010.Archivedfrom the original on 5 April 2018.Retrieved6 May2018.
- ^Jon B (11 February 2005)."Noodles, reinvented".NBC News.Retrieved2 April2008.
Further reading[edit]
- Akbari, et al. (2021)."Recent advances in microbial transglutaminase biosynthesis and its application in the food industry".Trends in Food Science & Technology.Retrieved31 August2023.
- Fesus L, Hitomi K, Kojima S (2015).Transglutaminases: Multiple Functional Modifiers and Targets for New Drug Discovery.Springer Japan.ISBN978-4-431-55823-1.
- Nuijens T, Schmidt M (2019).Enzyme-mediated ligation methods.Humana, New York, NY.ISBN978-1-4939-9545-5.
- Kuddus M (2018).Enzymes in food technology: improvements and innovations.Springer, Singapore.ISBN978-981-13-1932-7.
- Kelleher JB (11 May 2012)."Industry defends ingredient critics deride as" meat glue "".Chicago Tribune.Retrieved20 July2012.
- Marhons, et al. (2023)."Properties of yoghurt treated with microbial transglutaminase and exopolysaccharides".International Dairy Journal.Retrieved31 August2023.
- U.S. patent 5,156,956– 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+
