title: Structure of Bacillus subtilis γ-glutamyltranspeptidase in complex with acivicin: diversity of the binding mode of a classical and electrophilic active-site-directed glutamate analogue.
abstract: γ-Glutamyltranspeptidase (GGT) is an enzyme that plays a central role in glutathione metabolism, and acivicin is a classical inhibitor of GGT. Here, the structure of acivicin bound to Bacillus subtilis GGT determined by X-ray crystallography to 1.8 Å resolution is presented, in which it binds to the active site in a similar manner to that in Helicobacter pylori GGT, but in a different binding mode to that in Escherichia coli GGT. In B. subtilis GGT, acivicin is bound covalently through its C3 atom with sp2 hybridization to Thr403 Oγ, the catalytic nucleophile of the enzyme. The results show that acivicin-binding sites are common, but the binding manners and orientations of its five-membered dihydroisoxazole ring are diverse in the binding pockets of GGTs.
authors: Department of Biological Sciences, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan.
authors: Tomoyo
authors: T
authors: Ida
authors: Division of Applied Biology, Graduate School of Science and Technology, Kyoto Institute of Technology, Goshokaido-cho, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
authors: Hideyuki
authors: H
authors: Suzuki
authors: Department of Biological Sciences, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan.
authors: Keiichi
authors: K
authors: Fukuyama
authors: Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan.
authors: Jun
authors: J
authors: Hiratake
authors: Organization for Promotion of Tenure Track, University of Miyazaki, Miyazaki 889-1692, Japan.
authors: Kei
authors: K
authors: Wada
mesh_terms: D001412:Bacillus subtilis / Q000737:chemistry* / Q000201:enzymology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry*; D004926:Escherichia coli / Q000737:chemistry / Q000201:enzymology; D018698:Glutamic Acid / Q000737:chemistry; D016480:Helicobacter pylori / Q000737:chemistry / Q000201:enzymology; D007555:Isoxazoles / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D007555:Isoxazoles; D008024:Ligands; D011994:Recombinant Proteins; D018698:Glutamic Acid; D005723:gamma-Glutamyltransferase; C006303:acivicin
keywords: Ntn-hydrolase family; acivicin; glutamine amidotransferase; glutamine antagonist; glutathione; inhibitors; γ-glutamyltranspeptidase