Structure determination and refinement of human alpha class glutathione transferase A1-1, and a comparison with the Mu and Pi class enzymes.
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.
Sinning
I
I
Department of Molecular Biology, Uppsala University Biomedical Center, Sweden.
Kleywegt
G J
GJ
Cowan
S W
SW
Reinemer
P
P
Dirr
H W
HW
Huber
R
R
Gilliland
G L
GL
Armstrong
R N
RN
Ji
X
X
Board
P G
PG
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
D046911:Macromolecular Substances; D011994:Recombinant Proteins; D005982:Glutathione Transferase; D005978:Glutathione