title: Structure determination and refinement of human alpha class glutathione transferase A1-1, and a comparison with the Mu and Pi class enzymes.
abstract: The crystal structure of human alpha class glutathione transferase A1-1 has been determined and refined to a resolution of 2.6 A. There are two copies of the dimeric enzyme in the asymmetric unit. Each monomer is built from two domains. A bound inhibitor, S-benzyl-glutathione, is primarily associated with one of these domains via a network of hydrogen bonds and salt-links. In particular, the sulphur atom of the inhibitor forms a hydrogen bond to the hydroxyl group of Tyr9 and the guanido group of Arg15. The benzyl group of the inhibitor is completely buried in a hydrophobic pocket. The structure shows an overall similarity to the mu and pi class enzymes particularly in the glutathione-binding domain". The main difference concerns the extended C terminus of the alpha class enzyme which forms an extra alpha-helix that blocks one entrance to the active site and makes up part of the substrate binding site.
authors.affiliation: Department of Molecular Biology, Uppsala University Biomedical Center, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Sinning
authors.forename: G J
authors.initials: GJ
authors.lastname: Kleywegt
authors.forename: S W
authors.initials: SW
authors.lastname: Cowan
authors.forename: P
authors.initials: P
authors.lastname: Reinemer
authors.forename: H W
authors.initials: HW
authors.lastname: Dirr
authors.forename: R
authors.initials: R
authors.lastname: Huber
authors.forename: G L
authors.initials: GL
authors.lastname: Gilliland
authors.forename: R N
authors.initials: RN
authors.lastname: Armstrong
authors.forename: X
authors.initials: X
authors.lastname: Ji
authors.forename: P G
authors.initials: PG
authors.lastname: Board
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003461:Crystallography; D005978:Glutathione / Q000737:chemistry; D005982:Glutathione Transferase / Q000145:classification / Q000648:ultrastructure*; D006801:Humans; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins; D016415:Sequence Alignment; D012984:Software; D014961:X-Ray Diffraction
chemical_list: D046911:Macromolecular Substances; D011994:Recombinant Proteins; D005982:Glutathione Transferase; D005978:Glutathione