2PN7

Human gamma-glutamyl cyclotransferase

2PN7 の概要

• エントリーDOI: 10.2210/pdb2pn7/pdb
• 分子名称: human gamma-glutamyl cyclotransferase (2 entities in total)
• 機能のキーワード: beta barrel, dimer, human gamma-glutamyl cyclotransferase, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 42059.38

構造登録者

Oakley, A.J.,Board, P.G. (登録日: 2007-04-24, 公開日: 2007-05-01, 最終更新日: 2024-02-21)

主引用文献

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

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: 18515354
DOI: 10.1074/jbc.M803623200

実験手法

X-RAY DIFFRACTION (2.41 Å)