Division of Molecular and Health Technologies, Commonwealth Scientific and Industrial Research Organization, Parkville, Victoria 3052.
John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory 2601, Australia.
J Biol Chem. 2010 Mar 26;285(13):9642-9648. doi: 10.1074/jbc.M109.082099. Epub 2010 Jan 28.
Gamma-glutamylamine cyclotransferase (GGACT) is an enzyme that converts gamma-glutamylamines to free amines and 5-oxoproline. GGACT shows high activity toward gamma-glutamyl-epsilon-lysine, derived from the breakdown of fibrin and other proteins cross-linked by transglutaminases. The enzyme adopts the newly identified cyclotransferase fold, observed in gamma-glutamylcyclotransferase (GGCT), an enzyme with activity toward gamma-glutamyl-alpha-amino acids (Oakley, A. J., Yamada, T., Liu, D., Coggan, M., Clark, A. G., and Board, P. G. (2008) J. Biol. Chem. 283, 22031-22042). Despite the absence of significant sequence identity, several residues are conserved in the active sites of GGCT and GGACT, including a putative catalytic acid/base residue (GGACT Glu(82)). The structure of GGACT in complex with the reaction product 5-oxoproline provides evidence for a common catalytic mechanism in both enzymes. The proposed mechanism, combined with the three-dimensional structures, also explains the different substrate specificities of these enzymes. Despite significant sequence divergence, there are at least three subfamilies in prokaryotes and eukaryotes that have conserved the GGCT fold and GGCT enzymatic activity.
γ-谷氨酰胺环转移酶（GGACT）是一种酶，可将γ-谷氨酰胺转化为游离胺和 5-氧代脯氨酸。GGACT 对源自纤维蛋白和其他由转谷氨酰胺酶交联的蛋白质的 γ-谷氨酰-ε-赖氨酸具有高活性。该酶采用了新发现的环转移酶折叠，在 γ-谷氨酰环转移酶（GGCT）中观察到这种折叠，该酶对 γ-谷氨酰-α-氨基酸具有活性（Oakley，A. J.，Yamada，T.，Liu，D.，Coggan，M.，Clark，A. G.和 Board，P. G.（2008）J. Biol. Chem. 283，22031-22042）。尽管没有显著的序列同一性，但在 GGCT 和 GGACT 的活性位点中保守了几个残基，包括一个假定的催化酸碱残基（GGACT Glu（82））。与反应产物 5-氧代脯氨酸结合的 GGACT 结构为这两种酶提供了一个共同的催化机制的证据。该提议的机制，结合三维结构，也解释了这些酶的不同底物特异性。尽管存在显著的序列分歧，但原核生物和真核生物中至少有三个亚家族保留了 GGCT 折叠和 GGCT 酶活性。
