2DG5

Crystal Structure of Gamma-glutamyl transpeptidase from Escherichia coli in complex with hydrolyzed Glutathione

2DG5 の概要

• エントリーDOI: 10.2210/pdb2dg5/pdb
• 関連するPDBエントリー: 2DBU 2DBW 2DBX
• 分子名称: Gamma-glutamyltranspeptidase, GLYCEROL, CALCIUM ION, ... (6 entities in total)
• 機能のキーワード: gamma-glutamyltransferase, ggt, gamma-gt, glutathione, transferase
• 由来する生物種: Escherichia coli K12; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 120646.55

構造登録者

Okada, T.,Wada, K.,Fukuyama, K. (登録日: 2006-03-08, 公開日: 2006-04-18, 最終更新日: 2024-10-16)

主引用文献

Okada, T.,Suzuki, H.,Wada, K.,Kumagai, H.,Fukuyama, K.
Crystal structures of gamma-glutamyltranspeptidase from Escherichia coli, a key enzyme in glutathione metabolism, and its reaction intermediate.
Proc.Natl.Acad.Sci.Usa, 103:6471-6476, 2006

PubMed Abstract: Gamma-glutamyltranspeptidase (GGT) is a heterodimic enzyme that is generated from the precursor protein through posttranslational processing and catalyzes the hydrolysis of gamma-glutamyl bonds in gamma-glutamyl compounds such as glutathione and/or the transfer of the gamma-glutamyl group to other amino acids and peptides. We have determined the crystal structure of GGT from Escherichia coli K-12 at 1.95 A resolution. GGT has a stacked alphabetabetaalpha fold comprising the large and small subunits, similar to the folds seen in members of the N-terminal nucleophile hydrolase superfamily. The active site Thr-391, the N-terminal residue of the small subunit, is located in the groove, from which the pocket for gamma-glutamyl moiety binding follows. We have further determined the structure of the gamma-glutamyl-enzyme intermediate trapped by flash cooling the GGT crystal soaked in glutathione solution and the structure of GGT in complex with l-glutamate. These structures revealed how the gamma-glutamyl moiety and l-glutamate are recognized by the enzyme. A water molecule was seen on the carbonyl carbon of the gamma-glutamyl-Thr-391 Ogamma bond in the intermediate that is to be hydrolyzed. Notably the residues essential for GGT activity (Arg-114, Asp-433, Ser-462, and Ser-463 in E. coli GGT) shown by site-directed mutagenesis of human GGT are all involved in the binding of the gamma-glutamyl moiety. The structure of E. coli GGT presented here, together with sequence alignment of GGTs, may be applicable to interpret the biochemical and genetic data of other GGTs.

PubMed: 16618936
DOI: 10.1073/pnas.0511020103

実験手法

X-RAY DIFFRACTION (1.6 Å)