Transglutaminases (TGases) are Ca2+-dependent enzymes capable of catalysing transamidation of glutamine residues to form intermolecular isopeptide bonds. Nine distinct TGases have been described in mammals, and two of them (types 2 and 3) are regulated by GTP/ATP. TGase2 hydrolyses GTP and is therefore a bifunctional enzyme. In the present study, we report that TGase5 is also regulated by nucleotides. We have identified the putative TGase5 GTP-binding pocket by comparative amino acid sequence alignment and homology-derived three-dimensional modelling. GTP and ATP inhibit TGase5 cross-linking activity in vitro, and Ca2+ is capable of completely reversing this inhibition. In addition, TGase5 mRNA is not restricted to epidermal tissue, but is also present in different adult and foetal tissues, suggesting a role for TGase5 outside the epidermis. These results reveal the reciprocal actions of Ca2+ and nucleotides with respect to TGase5 activity. Taken together, these results indicate that TGases are a complex family of enzymes regulated by calcium, with at least three of them, namely TGase2, TGase3 and TGase5, also being regulated by ATP and GTP.
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Research Article|
June 22 2004
Transglutaminase 5 is regulated by guanine–adenine nucleotides1
Eleonora CANDI;
Eleonora CANDI
*Department of Experimental Medicine and Biochemical Sciences, Biochemistry LAb IDI-IRCCS, University of Rome Tor Vergata, via Montpellier 1, 00133 Rome, Italy
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Andrea PARADISI;
Andrea PARADISI
*Department of Experimental Medicine and Biochemical Sciences, Biochemistry LAb IDI-IRCCS, University of Rome Tor Vergata, via Montpellier 1, 00133 Rome, Italy
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Alessandro TERRINONI;
Alessandro TERRINONI
*Department of Experimental Medicine and Biochemical Sciences, Biochemistry LAb IDI-IRCCS, University of Rome Tor Vergata, via Montpellier 1, 00133 Rome, Italy
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Valentina PIETRONI;
Valentina PIETRONI
*Department of Experimental Medicine and Biochemical Sciences, Biochemistry LAb IDI-IRCCS, University of Rome Tor Vergata, via Montpellier 1, 00133 Rome, Italy
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Sergio ODDI;
Sergio ODDI
*Department of Experimental Medicine and Biochemical Sciences, Biochemistry LAb IDI-IRCCS, University of Rome Tor Vergata, via Montpellier 1, 00133 Rome, Italy
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Bruno CADOT;
Bruno CADOT
*Department of Experimental Medicine and Biochemical Sciences, Biochemistry LAb IDI-IRCCS, University of Rome Tor Vergata, via Montpellier 1, 00133 Rome, Italy
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Vishwanath JOGINI;
Vishwanath JOGINI
†Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, U.S.A.
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Muthuraman MEIYAPPAN;
Muthuraman MEIYAPPAN
†Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, U.S.A.
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Jon CLARDY;
Jon CLARDY
†Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, U.S.A.
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Alessandro FINAZZI-AGRO;
Alessandro FINAZZI-AGRO
*Department of Experimental Medicine and Biochemical Sciences, Biochemistry LAb IDI-IRCCS, University of Rome Tor Vergata, via Montpellier 1, 00133 Rome, Italy
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Gerry MELINO
Gerry MELINO
2
‡Medical Research Council Toxicology Unit, University of Leicester, Lancaster Rd, Leicester LE1 9HN, U.K.
2To whom correspondence should be addressed (e-mail gerry.melino@uniroma2.it).
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Publisher: Portland Press Ltd
Received:
September 26 2003
Revision Received:
March 16 2004
Accepted:
March 23 2004
Accepted Manuscript online:
March 23 2004
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2004
Biochem J (2004) 381 (1): 313–319.
Article history
Received:
September 26 2003
Revision Received:
March 16 2004
Accepted:
March 23 2004
Accepted Manuscript online:
March 23 2004
Citation
Eleonora CANDI, Andrea PARADISI, Alessandro TERRINONI, Valentina PIETRONI, Sergio ODDI, Bruno CADOT, Vishwanath JOGINI, Muthuraman MEIYAPPAN, Jon CLARDY, Alessandro FINAZZI-AGRO, Gerry MELINO; Transglutaminase 5 is regulated by guanine–adenine nucleotides. Biochem J 1 July 2004; 381 (1): 313–319. doi: https://doi.org/10.1042/BJ20031474
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