3juc | pdb_00003juc
Human gamma-glutamylamine cyclotransferase complex with 5-oxoproline
Structural highlights
Function[GGACT_HUMAN] Contributes to degradation of proteins cross-linked by transglutaminases. Degrades the cross-link between a lysine and a glutamic acid residue from two proteins that have been cross-linked by transglutaminases. Catalyzes the formation of 5-oxoproline from L-gamma-glutamyl-L-epsilon-lysine. Inactive with L-gamma-glutamyl-alpha-amino acid substrates such as L-gamma-glutamyl-L-alpha-cysteine and L-gamma-glutamyl-L-alpha-alanine.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedGamma-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. Identification and characterization of gamma-glutamylamine cyclotransferase, an enzyme responsible for gamma-glutamyl-epsilon-lysine catabolism.,Oakley AJ, Coggan M, Board PG J Biol Chem. 2010 Mar 26;285(13):9642-8. Epub 2010 Jan 28. PMID:20110353[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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