Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary extracted from

  • Siegel, M.; Khosla, C.
    Transglutaminase 2 inhibitors and their therapeutic role in disease states (2007), Pharmacol. Ther., 115, 232-245.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
2.3.2.13 medicine cystamine delays the onset of the neurological symptoms associated with Huntington’s disease when applied to the R6/2 Huntington’s mouse model, and dihydroisoxazoles, when used in tandem with BCNU, are able to decrease tumor size and extend survival in a mouse model of glioblastoma Mus musculus
2.3.2.13 medicine transglutaminase 2 is involved in the pathogenesis of a number of diseases, such as celiac sprue, neurodegenerative disorders, diabetes, liver cirrhosis and fibrosis, renal scarring, and certain types of cancer. It is the enzymatic function of TG2 that is thought to contribute to the pathology or etiology of most of the aforementioned diseases. Therefore, inhibition of the TG2 active site offers a potential strategy to therapeutically treat these disease Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.3.2.13 2-Iodoacetamide
-
Cavia porcellus
2.3.2.13 5-(biotinamido)pentylamine
-
Homo sapiens
2.3.2.13 cystamine
-
Homo sapiens
2.3.2.13 GDP
-
Homo sapiens
2.3.2.13 GTP causes significant shifts in electrophoretic mobility of the protein under native conditions Homo sapiens
2.3.2.13 Monodansylcadaverine
-
Homo sapiens
2.3.2.13 N-[(3-bromo-4,5-dihydroisoxazol-5-yl)methyl]-5-fluoro-Na-[(quinolin-3-ylmethoxy)carbonyl]-L-tryptophanamide
-
Homo sapiens
2.3.2.13 N-[(3-bromo-4,5-dihydroisoxazol-5-yl)methyl]-5-fluoro-Na-[(quinolin-3-ylmethoxy)carbonyl]tryptophanamide
-
Homo sapiens
2.3.2.13 N-[(6Z)-8-amino-2-[[(benzyloxy)carbonyl]amino]-8-oxooct-6-enoyl]glycine
-
Cavia porcellus
2.3.2.13 N-[[(5S)-3-bromo-4,5-dihydroisoxazol-5-yl]methyl]-5-fluoro-Na-[(quinolin-3-ylmethoxy)carbonyl]-L-tryptophanamide
-
Homo sapiens
2.3.2.13 Na-[(benzyloxy)carbonyl]-N-[(3-bromo-4,5-dihydroisoxazol-5-yl)methyl]-5-fluorotryptophanamide
-
Homo sapiens
2.3.2.13 Nalpha-[(benzyloxy)carbonyl]-N-[(3-bromo-4,5-dihydroisoxazol-5-yl)methyl]-L-tyrosinamide
-
Homo sapiens
2.3.2.13 putrescine
-
Homo sapiens
2.3.2.13 quinolin-3-ylmethyl [(1S)-2-([[(5S)-3-bromo-4,5-dihydroisoxazol-5-yl]methyl]amino)-1-(4-hydroxybenzyl)-2-oxoethyl]carbamate
-
Homo sapiens
2.3.2.13 quinolin-3-ylmethyl [(1S)-2-[[(3-bromo-4,5-dihydroisoxazol-5-yl)methyl]amino]-1-(4-hydroxybenzyl)-2-oxoethyl]carbamate
-
Homo sapiens
2.3.2.13 [(2-[[(benzyloxy)carbonyl]amino]-4-[5-(formylamino)-1,2,4-thiadiazol-3-yl]butanoyl)amino]acetic acid
-
Cavia porcellus
2.3.2.13 [(4-[3-(aminocarbonyl)oxiran-2-yl]-2-[[(benzyloxy)carbonyl]amino]butanoyl)amino]acetic acid
-
Cavia porcellus
2.3.2.13 [([3-(aminocarbonyl)oxiran-2-yl][[(benzyloxy)carbonyl]amino]acetyl)amino]acetic acid
-
Cavia porcellus
2.3.2.13 [[(4E)-6-amino-2-[[(benzyloxy)carbonyl]amino]-6-oxohex-4-enoyl]amino]acetic acid
-
Cavia porcellus
2.3.2.13 [[(5E)-7-amino-2-[[(benzyloxy)carbonyl]amino]-7-oxohept-5-enoyl]amino]acetic acid
-
Cavia porcellus
2.3.2.13 [[(6Z)-8-amino-2-[[(benzyloxy)carbonyl]amino]-8-oxooct-6-enoyl]amino]acetic acid
-
Cavia porcellus

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.3.2.13 cytosol
-
Homo sapiens 5829
-
2.3.2.13 extracellular
-
Homo sapiens
-
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.3.2.13 Ca2+ required Homo sapiens

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
2.3.2.13 additional information
-
TG2 can assume multiple conformations Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.3.2.13 additional information Homo sapiens functions of TG2: wound healing, macrophage phagocytosis, TGF-beta activation, protein kinase activity, association with calreticulin, and association with G-protein coupled receptor GPR56. The majority of these functions are independent of the enzymatic transamidation activity of the protein. Transglutaminase 2 is involved in the pathogenesis of a number of diseases, such as celiac sprue, neurodegenerative disorders, diabetes, liver cirrhosis and fibrosis, renal scarring, and certain types of cancer. It is the enzymatic function of TG2 that is thought to contribute to the pathology or etiology of most of the aforementioned diseases ?
-
?

Organism

EC Number Organism UniProt Comment Textmining
2.3.2.13 Cavia porcellus
-
-
-
2.3.2.13 Homo sapiens
-
-
-
2.3.2.13 Mus musculus
-
-
-

Reaction

EC Number Reaction Comment Organism Reaction ID
2.3.2.13 protein glutamine + alkylamine = protein N5-alkylglutamine + NH3 the first step in both types of modifications is the acylation of the active site cysteine (Cys277) of TG2 by a protein-bound glutamine residue, resulting in the liberation of ammonia and the formation of a thioester intermediate between TG2 and the glutamine bearing protein substrate. In TG2 catalyzed transamidation, the thioester intermediate is attacked by a nucleophilic primary amine, either a small molecule amine such as putrescine or the epsilon-amino group of protein-bound lysine residues. This results in the formation of relatively stable isopeptide bonds Homo sapiens

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.3.2.13 additional information TG2 shows an ubiquitous expression pattern of this protein throughout the body Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.2.13 additional information functions of TG2: wound healing, macrophage phagocytosis, TGF-beta activation, protein kinase activity, association with calreticulin, and association with G-protein coupled receptor GPR56. The majority of these functions are independent of the enzymatic transamidation activity of the protein. Transglutaminase 2 is involved in the pathogenesis of a number of diseases, such as celiac sprue, neurodegenerative disorders, diabetes, liver cirrhosis and fibrosis, renal scarring, and certain types of cancer. It is the enzymatic function of TG2 that is thought to contribute to the pathology or etiology of most of the aforementioned diseases Homo sapiens ?
-
?

Synonyms

EC Number Synonyms Comment Organism
2.3.2.13 TG2
-
Cavia porcellus
2.3.2.13 TG2
-
Mus musculus
2.3.2.13 TG2
-
Homo sapiens
2.3.2.13 transglutaminase 2
-
Cavia porcellus
2.3.2.13 transglutaminase 2
-
Mus musculus
2.3.2.13 transglutaminase 2
-
Homo sapiens

pH Range

EC Number pH Minimum pH Maximum Comment Organism
2.3.2.13 additional information
-
the transamidation reaction is kinetically favored over deamidation at pH-values above 7, but the deamidation reaction becomes kinetically competitive as the pH is lowered below 7 or as the concentration of amine substrates is lowered below their Km values Homo sapiens

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
2.3.2.13 0.000075
-
2-Iodoacetamide
-
Cavia porcellus
2.3.2.13 0.00028
-
[[(6Z)-8-amino-2-[[(benzyloxy)carbonyl]amino]-8-oxooct-6-enoyl]amino]acetic acid
-
Cavia porcellus
2.3.2.13 0.00048
-
[[(5E)-7-amino-2-[[(benzyloxy)carbonyl]amino]-7-oxohept-5-enoyl]amino]acetic acid
-
Cavia porcellus
2.3.2.13 0.00056
-
[([3-(aminocarbonyl)oxiran-2-yl][[(benzyloxy)carbonyl]amino]acetyl)amino]acetic acid
-
Cavia porcellus
2.3.2.13 0.0011
-
N-[(6Z)-8-amino-2-[[(benzyloxy)carbonyl]amino]-8-oxooct-6-enoyl]glycine
-
Cavia porcellus
2.3.2.13 0.00123
-
[(4-[3-(aminocarbonyl)oxiran-2-yl]-2-[[(benzyloxy)carbonyl]amino]butanoyl)amino]acetic acid
-
Cavia porcellus
2.3.2.13 0.0013
-
N-[[(5S)-3-bromo-4,5-dihydroisoxazol-5-yl]methyl]-5-fluoro-Na-[(quinolin-3-ylmethoxy)carbonyl]-L-tryptophanamide
-
Homo sapiens
2.3.2.13 0.00275
-
[[(4E)-6-amino-2-[[(benzyloxy)carbonyl]amino]-6-oxohex-4-enoyl]amino]acetic acid
-
Cavia porcellus
2.3.2.13 0.004
-
N-[(3-bromo-4,5-dihydroisoxazol-5-yl)methyl]-5-fluoro-Na-[(quinolin-3-ylmethoxy)carbonyl]-L-tryptophanamide
-
Homo sapiens
2.3.2.13 0.014
-
[(2-[[(benzyloxy)carbonyl]amino]-4-[5-(formylamino)-1,2,4-thiadiazol-3-yl]butanoyl)amino]acetic acid
-
Cavia porcellus
2.3.2.13 0.018
-
N-[(3-bromo-4,5-dihydroisoxazol-5-yl)methyl]-5-fluoro-Na-[(quinolin-3-ylmethoxy)carbonyl]tryptophanamide
-
Homo sapiens
2.3.2.13 0.019
-
Na-[(benzyloxy)carbonyl]-N-[(3-bromo-4,5-dihydroisoxazol-5-yl)methyl]-5-fluorotryptophanamide
-
Homo sapiens
2.3.2.13 0.03
-
quinolin-3-ylmethyl [(1S)-2-([[(5S)-3-bromo-4,5-dihydroisoxazol-5-yl]methyl]amino)-1-(4-hydroxybenzyl)-2-oxoethyl]carbamate
-
Homo sapiens
2.3.2.13 0.041
-
quinolin-3-ylmethyl [(1S)-2-[[(3-bromo-4,5-dihydroisoxazol-5-yl)methyl]amino]-1-(4-hydroxybenzyl)-2-oxoethyl]carbamate
-
Homo sapiens
2.3.2.13 0.42
-
Nalpha-[(benzyloxy)carbonyl]-N-[(3-bromo-4,5-dihydroisoxazol-5-yl)methyl]-L-tyrosinamide
-
Homo sapiens

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
2.3.2.13 0.009
-
-
Homo sapiens GTP