2RBH: Gamma-glutamyl Cyclotransferase

Citation:
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.
PDB ID: 2RBHDownload
MMDB ID: 59689
PDB Deposition Date: 2007/9/19
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.1  Å
Source Organism:
Similar Structures:
Biological Unit for 2RBH: dimeric; determined by author and by software (PISA)
Molecular Components in 2RBH
Label Count Molecule
Proteins (2 molecules)
2
Gamma-glutamyl Cyclotransferase(Gene symbol: GGCT)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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