Transglutaminase 5 is regulated by guanine-adenine nucleotides
- Biochem J. 2004 Jul 1;381(Pt 1):313-9. doi: 10.1042/BJ20031474.
- 1. Department of Experimental Medicine and Biochemical Sciences, Biochemistry LAb IDI-IRCCS, University of Rome Tor Vergata, via Montpellier 1, 00133 Rome, Italy.
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.