Transglutaminase 5 is regulated by guanine-adenine nucleotides
Transglutaminase 5 is regulated by guanine-adenine nucleotides
复制标题
DOI：
10.1042/bj20031474
复制
发表时间：
2004-07-01
影响因子：
4.1
通讯作者：
Melino, G
中科院分区：
文献类型：
--
作者：
Candi, E;Paradisi, A;Melino, G
转谷氨酰胺酶（TGases）是能够催化谷氨酰胺残基的转酰胺作用以形成分子间异肽键的Ca 2+依赖性酶。在哺乳动物中已经描述了九种不同的TGases，其中两种（2型和3型）由GTP/ATP调节。TGase 2水解GTP，因此是双功能酶。在本研究中，我们报告，TGase 5也受到核苷酸的调控。我们已经确定了推定的TGase 5 GTP结合口袋比较氨基酸序列比对和同源衍生的三维建模。GTP和ATP在体外抑制TGase 5交联活性，并且Ca 2+能够完全逆转这种抑制。此外，TGase 5 mRNA不限于表皮组织，但也存在于不同的成人和胎儿组织中，表明TGase 5在表皮外的作用。这些结果揭示了Ca 2+和核苷酸对TGase 5活性的相互作用。综上所述，这些结果表明，TGases是一个复杂的酶家族，由钙调节，其中至少有三个，即TGase 2，TGase 3和TGase 5，也由ATP和GTP调节。
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.