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.

Nyckelord

Amino Acid Sequence

Binding Sites

Crystallography

Glutathione/chemistry

Glutathione Transferase/classification/*ultrastructure

Humans

Macromolecular Substances

Models; Molecular

Molecular Sequence Data

Mutagenesis; Site-Directed

Protein Structure; Secondary

Protein Structure; Tertiary

Recombinant Proteins

Sequence Alignment

Software

X-Ray Diffraction

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