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PDBsum entry 1m9a
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Characterization of the electrophile binding site and substrate binding mode of the 26-Kda glutathione s-Transferase from schistosoma japonicum.
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Authors
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R.M.Cardoso,
D.S.Daniels,
C.M.Bruns,
J.A.Tainer.
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Ref.
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Proteins, 2003,
51,
137-146.
[DOI no: ]
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PubMed id
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Abstract
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The 26-kDa glutathione S-transferase from Schistosoma japonicum (Sj26GST), a
helminth worm that causes schistosomiasis, catalyzes the conjugation of
glutathione with toxic secondary products of membrane lipid peroxidation.
Crystal structures of Sj26GST in complex with glutathione sulfonate
(Sj26GSTSLF), S-hexyl glutathione (Sj26GSTHEX), and S-2-iodobenzyl glutathione
(Sj26GSTIBZ) allow characterization of the electrophile binding site (H site) of
Sj26GST. The S-hexyl and S-2-iodobenzyl moieties of these product analogs bind
in a pocket defined by side-chains from the beta1-alpha1 loop (Tyr7, Trp8,
Ile10, Gly12, Leu13), helix alpha4 (Arg103, Tyr104, Ser107, Tyr111), and the
C-terminal coil (Gln204, Gly205, Trp206, Gln207). Changes in the Ser107 and
Gln204 dihedral angles make the H site more hydrophobic in the Sj26GSTHEX
complex relative to the ligand-free structure. These structures, together with
docking studies, indicate a possible binding mode of Sj26GST to its physiologic
substrates 4-hydroxynon-2-enal (4HNE), trans-non-2-enal (NE), and ethacrynic
acid (EA). In this binding mode, hydrogen bonds of Tyr111 and Gln207 to the
carbonyl oxygen atoms of 4HNE, NE, and EA could orient the substrates and
enhance their electrophilicity to promote conjugation with glutathione.
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Figure 1.
Figure 1. Binding of product analogs to the H and G sites of
Sj26GST.  A-weighted
Fo - Fc electron density, contoured at 3.0 ,
is shown for the ligands (glutathione in brown, S-hexyl and
S-2-iodobenzyl in yellow). Functionally important H site
residues are shown in purple. (A) Glutathione sulfonate. Tyr7
and a water molecule participate in a hydrogen bond with the
sulfonate. (B) S-hexyl glutathione. Tyr7, Gly12, Leu13, Arg103,
Ser107, Tyr111, and Gln204 participate in the S-hexyl moiety
binding to the H site. (C) S-2-Iodobenzyl glutathione. Tyr7,
Leu13, Ser107, and Tyr111 participate in binding the
2-iodobenzyl moiety at the H site.
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Figure 3.
Figure 3. Superposition of the Sj26GST and hGST A4-4 H sites.
Functionally important H site residues of Sj26GST (pink trace
and yellow side-chains) and hGST A4-4 (blue trace pink and green
side-chains) are shown. The C-terminal coil of Sj26GST adopts an
 -helical
structure in A4-4.
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The above figures are
reprinted
by permission from John Wiley & Sons, Inc.:
Proteins
(2003,
51,
137-146)
copyright 2003.
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Secondary reference #1
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Title
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Crystal structures of a schistosomal drug and vaccine target: glutathione s-Transferase from schistosoma japonica and its complex with the leading antischistosomal drug praziquantel.
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Authors
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M.A.Mctigue,
D.R.Williams,
J.A.Tainer.
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Ref.
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J Mol Biol, 1995,
246,
21-27.
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PubMed id
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Secondary reference #2
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Title
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Three-Dimensional structure of schistosoma japonicum glutathione s-Transferase fused with a six-Amino acid conserved neutralizing epitope of gp41 from HIV.
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Authors
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K.Lim,
J.X.Ho,
K.Keeling,
G.L.Gilliland,
X.Ji,
F.Rüker,
D.C.Carter.
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Ref.
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Protein Sci, 1994,
3,
2233-2244.
[DOI no: ]
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PubMed id
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