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The three-dimensional structure of class pi glutathione S-transferase from pig
lung, a homodimeric enzyme, has been solved by multiple isomorphous replacement
at 3 A resolution and preliminarily refined at 2.3 A resolution (R = 0.24). Each
subunit (207 residues) is folded into two domains of different structure. Domain
I (residues 1-74) consists of a central four-stranded beta-sheet flanked on one
side by two alpha-helices and on the other side, facing the solvent, by a bent,
irregular helix structure. The topological pattern resembles the bacteriophage
T4 thioredoxin fold, in spite of their dissimilar sequences. Domain II (residues
81-207) contains five alpha-helices. The dimeric molecule is globular with
dimensions of about 55 A x 52 A x 45 A. Between the subunits and along the local
diad, is a large cavity which could possibly be involved in the transport of
nonsubstrate ligands. The binding site of the competitive inhibitor, glutathione
sulfonate, is located on domain I, and is part of a cleft formed between
intrasubunit domains. Glutathione sulfonate is bound in an extended conformation
through multiple interactions. Only three contact residues, namely Tyr7, Gln62
and Asp96 are conserved within the family of cytosolic glutathione
S-transferases. The exact location of the binding site(s) of the electrophilic
substrate is not clear. Catalytic models are discussed on the basis of the
molecular structure.
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