GTP hydrolysis by guinea pig liver transglutaminase

Lee, Kyung N.; Birckbichler, Paul J.; Patterson, M. K.

doi:10.1016/0006-291x(89)90825-5

Cited by 101 publications

(75 citation statements)

References 21 publications

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“…The redox catalyst Cu(II)(1,10-phenanthroline) 3 (made by diluting 20 mM CuSO 4 /20 mM 1,10-phenanthroline in buffer) was used to trigger oxidation by ambient dissolved oxygen (33).…”

Section: Methodsmentioning

confidence: 99%

Mechanism of allosteric regulation of transglutaminase 2 by GTP

Begg

Carrington

Stokes

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

138

145

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Allosteric regulation is a fundamental mechanism of biological control. Here, we investigated the allosteric mechanism by which GTP inhibits cross-linking activity of transglutaminase 2 (TG2), a multifunctional protein, with postulated roles in receptor signaling, extracellular matrix assembly, and apoptosis. Our findings indicate that at least two components are involved in functionally coupling the allosteric site and active center of TG2, namely (i) GTP binding to mask a conformationally destabilizing switch residue, Arg-579, and to facilitate interdomain interactions that promote adoption of a compact, catalytically inactive conformation and (ii) stabilization of the inactive conformation by an uncommon H bond between a cysteine (Cys-277, an active center residue) and a tyrosine (Tyr-516, a residue located on a loop of the ␤-barrel 1 domain that harbors the GTP-binding site). Although not essential for GTP-mediated inhibition of cross-linking, this H bond enhances the rate of formation of the inactive conformer.protein conformation ͉ GTP inhibition ͉ transamidase activity A llosteric regulation of enzymes by conformational change is an important means of biological control, involving residues that functionally couple ligand binding at the allosteric site to modification of the catalytic site. Transglutaminase type 2 (TG2), also known as tissue TG or G h (high molecular weight GTP-binding protein), is a multifunctional protein that is allosterically regulated by calcium and GTP (1). TG2 catalyzes calcium-dependent transamidation reactions, resulting in posttranslational amine modification of proteins or cross-linking of interchain glutamine and lysine residues to form N (␥-glutamyl)lysine isopeptide bonds, which confer rigidity and protease resistance on protein complexes (2). TG2 is also a GTPase (3) and mediates intracellular signaling by various G protein-coupled receptors (4-6).GDP-bound human TG2 (7) is comprised of four domains: an N-terminal ␤-sandwich, a core domain in which the transamidase active site catalytic triad (Cys-277, His-335, and Asp-358) and transition-state stabilizing residue (Trp-241) (8) are buried and inaccessible to substrate, and two ␤-barrels. Nucleotide binds mainly to residues from the first and last strands (amino acids 476-482 and 580-583) of ␤-barrel 1 and to two core domain residues (Lys-173 and Phe-174) that protrude on a loop to meet ␤-barrel 1 (7, 9, 10). This is postulated to stabilize two ␤-barrel 1 loops that block access to the catalytic site (7). One of these loops protrudes into the core domain localizing Tyr-516 within hydrogen-bonding distance of Cys-277 (7). This is postulated to prevent Cys-277 interaction with the substrate (7,11,12). Calcium-activated TG2 has unique conformational epitopes (13) and is less compact (14-16) and less resistant to protease digestion (1, 10, 14) than GTP-bound TG2. Allosteric mechanisms governing the conformational switch between transamidase and GTPase functions have yet to be elucidated.Mutation of Arg-579 in rat TG2 (Arg-580 in ...

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“…The redox catalyst Cu(II)(1,10-phenanthroline) 3 (made by diluting 20 mM CuSO 4 /20 mM 1,10-phenanthroline in buffer) was used to trigger oxidation by ambient dissolved oxygen (33).…”

Section: Methodsmentioning

confidence: 99%

Mechanism of allosteric regulation of transglutaminase 2 by GTP

Begg

Carrington

Stokes

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

138

145

View full text Add to dashboard Cite

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“…In addition to crosslinking activity, the enzyme has some other properties such as GTP binding and GTP hydrolysing activities, which are closely related with the signal transduction system (Lee et al, 1989). In cardiac myocyte, TGase C was identified to be Gh protein mediating the α1 adrenergic receptor signal to phospholipase C (Nakaoka et al, 1994).…”

Section: Five Different Types Of Tgases From the Mammalian 181mentioning

confidence: 99%

“…In addition, the enzyme has GTP-binding and GTPase activity (Lee et al, 1989), related with signal transduction system as Gh protein between α 1 adrenergic receptor and phospholipase C, influencing the neural functions (Nakaoka, 1994, Whang et al, 1995. Therefore, the regulation of TGase activity either as a crosslinker or as a signal transducer would be very important in functional, developmental and pathogenetic aspects of nervous system.…”

Section: Introductionmentioning

confidence: 99%

Isolation and characterization of brain-specific transglutaminases from rat

Kwak

Kim²,

Kim³

et al. 1998

Exp Mol Med

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The relevance of transglutaminases with neural function and several disorders has been emphasized recently. Especially, many polypeptides associated with neurodegenerative diseases are suggested to be putative transglutaminase substrates such as amyloid protein of Altzheimer's disease, microtubule-associated proteins and neurofilaments, etc. In addition, the CAG repeated gene products with probable polyglutamine tract, putative transglutami-nase substrates, were identified in several neuro-degenerative disorders. However, the identity of the brain transglutaminase has not been confirmed, because of enzymic stability and low activity. In the present experiment, we have isolated brain-specific transglutaminases, designated as TGase NI and TGase NII, which are different from other types of transglutaminases in respects of molecular weights (mw. 45 kDa, 29 kDa respectively), substrate affinity, elution profile on ion-exchange chromatography, sensitivity to proteases and ethanol, and immuno-logical properties. The enzymes were localized specifically in the brain tissues but not in the liver tissue. And neural cells such as pheochromocytoma cell, glioma cell, primary neuronal and glial cells were shown to be enriched with TGase NI and TGase NII. The possible biological roles of the enzymes were discussed not only on the aspect of crosslinking activity but also of signal transducing capacity of the enzyme in the brain. K e y w o r d s : TGase NI, TGaase NII, brain, rat, localization

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“…Several TG members are involved in diverse biological functions, such as blood coagulation, wound healing, cell envelope formation in keratinocyte differentiation, apoptosis, cell differentiation, cell adhesion, and the stiffening of the erythrocyte membrane. [2][3][4][5] Basically, the function of an enzyme is to catalyze the reaction which modifies a specific substrate to obtain a product, but the members of TG family appear to catalyze several different reactions, such as transamidation 2,5,6) including deamidation, 7,8) serotonylation, 9) and pegylation, 10) GTP-binding/hydrolyzation, [11][12][13] protein disulfide isomerization, [14][15][16] and kination. 17) Most of these catalytic functions are manifested by TG2 (tissuetype).…”

mentioning

confidence: 99%

Identification of New Amine Acceptor Protein Substrate Candidates of Transglutaminase in Rat Liver Extract: Use of 5-(Biotinamido) Pentylamine as a Probe

Ichikawa

Ishizaki

Morita

et al. 2008

Bioscience, Biotechnology, and Biochemistry

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Transglutaminases (TGs) are a family of enzymes that catalyze Ca 2þ -dependent post-translational modification of proteins by introducing protein-protein crosslinks (between specific glutamine and lysine residues), amine incorporation, and site-specific deamidation. In this study, new amine acceptor protein substrates of TG were isolated from rat liver extract and identified using 5-(biotinamido) pentylamine, a biotinylated primary amine substrate, as a probe. TG protein substrate candidates labeled with biotin by endogenous TG activity were isolated and recovered by avidin column chromatography. Proteins with molecular masses of 40, 42, and 45 kDa were the main components of the labeled proteins. Determination of their partial amino acid sequences and immunoblotting analyses were done to identify them. The 45-kDa protein was identical with betaine-homocysteine S-methyltransferase (EC 2.2.2.5), which was identified in our previous study. The 40-and 42-kDa proteins were identified as arginase-I (EC 3.5.3.1) and fructose-1,6-bisphosphatase (EC 3.1.3.11) respectively. TG catalyzed incorporation of 5-(biotinamido) pentylamine into both arginase-I and fructose-1,6-bisphosphatase purified from rat liver was confirmed in vitro. These results suggest that these two enzymes are the new protein substrate candidates of TG and that they can be modified post-translationally by cellular TG.

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GTP hydrolysis by guinea pig liver transglutaminase

Cited by 101 publications

References 21 publications

Mechanism of allosteric regulation of transglutaminase 2 by GTP

Mechanism of allosteric regulation of transglutaminase 2 by GTP

Isolation and characterization of brain-specific transglutaminases from rat

Identification of New Amine Acceptor Protein Substrate Candidates of Transglutaminase in Rat Liver Extract: Use of 5-(Biotinamido) Pentylamine as a Probe

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