Document Detail


Identification and characterization of gamma-glutamylamine cyclotransferase, an enzyme responsible for gamma-glutamyl-epsilon-lysine catabolism.
MedLine Citation:
PMID:  20110353     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Aaron J Oakley; Marjorie Coggan; Philip G Board
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-28
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-22     Completed Date:  2010-04-26     Revised Date:  2011-07-27    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9642-8     Citation Subset:  IM    
Affiliation:
Division of Molecular and Health Technologies, Commonwealth Scientific and Industrial Research Organization, Parkville, Victoria 3052, Australia.
Data Bank Information
Bank Name/Acc. No.:
PDB/3JUB;  3JUC;  3JUD
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Catalysis
Catalytic Domain
Cell Line, Tumor
Cloning, Molecular
Cross-Linking Reagents / chemistry
Crystallography, X-Ray / methods
Dipeptides / chemistry*
Gene Expression Regulation, Enzymologic*
Gene Expression Regulation, Neoplastic*
Humans
Molecular Sequence Data
Mutagenesis, Site-Directed
Protein Conformation
Pyrrolidonecarboxylic Acid / chemistry
Sequence Homology, Amino Acid
gamma-Glutamylcyclotransferase / chemistry*,  genetics*
Chemical
Reg. No./Substance:
0/Cross-Linking Reagents; 0/Dipeptides; 17105-15-6/epsilon-(gamma-glutamyl)-lysine; 98-79-3/Pyrrolidonecarboxylic Acid; EC 2.3.2.4/gamma-Glutamylcyclotransferase
Comments/Corrections

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