2RBH
Gamma-glutamyl cyclotransferase
Summary for 2RBH
| Entry DOI | 10.2210/pdb2rbh/pdb |
| Related | 2PN7 |
| Descriptor | Gamma-glutamyl cyclotransferase (2 entities in total) |
| Functional Keywords | cyclotransferase, enzyme, dimer, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 41943.31 |
| Authors | Oakley, A.J.,Board, P.G. (deposition date: 2007-09-19, release date: 2007-10-02, Last modification date: 2023-10-25) |
| Primary citation | Oakley, A.J.,Yamada, T.,Liu, D.,Coggan, M.,Clark, A.G.,Board, P.G. The identification and structural characterization of C7orf24 as gamma-glutamyl cyclotransferase. An essential enzyme in the gamma-glutamyl cycle J.Biol.Chem., 283:22031-22042, 2008 Cited by PubMed Abstract: The hypothetical protein C7orf24 has been implicated as a cancer marker with a potential role in cell proliferation. We have identified C7orf24 as gamma-glutamyl cyclotransferase (GGCT) that catalyzes the formation of 5-oxoproline (pyroglutamic acid) from gamma-glutamyl dipeptides and potentially plays a significant role in glutathione homeostasis. In the present study we have identified the first cDNA clones encoding a gamma-glutamyl cyclotransferase. The GGCT gene is located on chromosome 7p14-15 and consists of four exons that span 8 kb. The primary sequence is 188 amino acids in length and is unlike any protein of known function. We crystallized functional recombinant gamma-glutamyl cyclotransferase and determined its structure at 1.7 A resolution. The enzyme is a dimer of 20,994-Da subunits. The topology of GGCT is unrelated to other enzymes associated with cyclotransferase-like activity. The fold was originally classified as "BtrG-like," a small family that only includes structures of hypothetical proteins from Mus musculus, Escherichia coli, Pyrococcus horikoshii, and Arabidopsis thaliana. Since this is the first member of this family with a defined function, we propose to refer to this structure as the gamma-glutamyl cyclotransferase fold. We have identified a potential active site pocket that contains a highly conserved glutamic acid (Glu(98)) and propose that it acts as a general acid/base in the reaction mechanism. Mutation of Glu(98) to Ala or Gln completely inactivates the enzyme without altering the overall fold. PubMed: 18515354DOI: 10.1074/jbc.M803623200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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