1a0f | pdb_00001a0f
CRYSTAL STRUCTURE OF GLUTATHIONE S-TRANSFERASE FROM ESCHERICHIA COLI COMPLEXED WITH GLUTATHIONESULFONIC ACID
Structural highlights
Function[GSTA_ECOLI] Catalyzes the conjugation of reduced glutathione (GSH) to a wide number of exogenous and endogenous hydrophobic electrophiles. Shows activity toward 1-chloro-2,4-dinitrobenzene (CDNB) and ethacrynic acid. Also possesses thiol:disulfide oxidoreductase activity, using GSH to reduce bis-(2-hydroxyethyl) disulfide (HEDS). Has a low level of glutathione-dependent peroxidase activity toward cumene hydroperoxide. Is important for defense against oxidative stress, probably via its peroxidase activity.[1] [2] [3] [4] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedCytosolic glutathione S-transferase is a family of multi-functional enzymes involved in the detoxification of a large variety of xenobiotic and endobiotic compounds through glutathione conjugation. The three-dimensional structure of Escherichia coli glutathione S-transferase complexed with glutathione sulfonate, N-(N-L-gamma-glutamyl-3-sulfo-L-alanyl)-glycine, has been determined by the multiple isomorphous replacement method and refined to a crystallographic R factor of 0.183 at 2.1 A resolution. The E. coli enzyme is a globular homodimer with dimensions of 58 Ax56 Ax52 A. Each subunit, consisting of a polypeptide of 201 amino acid residues, is divided into a smaller N-terminal domain (residues 1 to 80) and a larger C-terminal one (residues 89 to 201). The core of the N-terminal domain is constructed by a four-stranded beta-sheet and two alpha-helices, and that of the C-terminal one is constructed by a right-handed bundle of four alpha-helices. Glutathione sulfonate, a competitive inhibitor against glutathione, is bound in a cleft between the N and C-terminal domains. Therefore, the E. coli enzyme conserves overall constructions common to the eukaryotic enzymes, in its polypeptide fold, dimeric assembly, and glutathione-binding site. In the case of the eukaryotic enzymes, tyrosine and serine residues near the N terminus are located in the proximity of the sulfur atom of the bound glutathione, and are proposed to be catalytically essential. In the E. coli enzyme, Tyr5 and Ser11 corresponding to these residues are not involved in the interaction with the inhibitor, although they are located in the vicinity of catalytic site. Instead, Cys10 N and His106 Nepsilon2 atoms are hydrogen-bonded to the sulfonate group of the inhibitor. On the basis of this structural study, Cys10 and His106 are ascribed to the catalytic residues that are distinctive from the family of the eukaryotic enzymes. We propose that glutathione S-transferases have diverged from a common origin and acquired different catalytic apparatuses in the process of evolution. Three-dimensional structure of Escherichia coli glutathione S-transferase complexed with glutathione sulfonate: catalytic roles of Cys10 and His106.,Nishida M, Harada S, Noguchi S, Satow Y, Inoue H, Takahashi K J Mol Biol. 1998 Aug 7;281(1):135-47. PMID:9680481[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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