Three-Dimensional structure of schistosoma japonicum glutathione s-transferase fused with a six-amino acid conserved neutralizing epitope of gp41 from hiv

The 3-dimensional crystal structure of glutathione S-transferase (GST) of Schistosoma japonicum (Sj) fused with a conserved neutralizing epitope on gp41 (glycoprotein, 41 kDa) of human immunodeficiency virus type 1 (HIV-1) (Muster T et al., 1993, J Virol 67:6642–6647) was determined at 2.5 Å resolution. The structure of the 3-3 isozyme rat GST of the μ gene class (Ji X, Zhang P, Armstrong RN, Gilliland GL, 1992, Biochemistry 31:10169–10184) was used as a molecular replacement model. The structure consists of a 4-stranded β-sheet and 3 α-helices in domain 1 and 5 α-helices in domain 2. The space group of the Sj GST crystal is P4₃2₁2, with unit cell dimensions of a = b = 94.7 Å, and c = 58.1 Å. The crystal has 1 GST monomer per asymmetric unit, and 2 monomers that form an active dimer are related by crystallographic 2-fold symmetry. In the binding site, the ordered structure of reduced glutathione is observed. The gp41 peptide (Glu-Leu-Asp-Lys-Trp-Ala) fused to the C-terminus of Sj GST forms a loop stabilized by symmetry-related GSTs. The Sj GST structure is compared with previously determined GST structures of mammalian gene classes μ, α, and π. Conserved amino acid residues among the 4 GSTs that are important for hydrophobic and hydrophilic interactions for dimer association and glutathione binding are discussed.