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PDBsum entry 2pgt
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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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Structure and function of the xenobiotic substrate-Binding site and location of a potential non-Substrate-Binding site in a class pi glutathione s-Transferase.
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Authors
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X.Ji,
M.Tordova,
R.O'Donnell,
J.F.Parsons,
J.B.Hayden,
G.L.Gilliland,
P.Zimniak.
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Ref.
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Biochemistry, 1997,
36,
9690-9702.
[DOI no: ]
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PubMed id
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Abstract
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Complex structures of a naturally occurring variant of human class pi
glutathione S-transferase 1-1 (hGSTP1-1) with either S-hexylglutathione or
(9R,10R)-9-(S-glutathionyl)-10-hydroxy-9, 10-dihydrophenanthrene
[(9R,10R)-GSPhen] have been determined at resolutions of 1.8 and 1.9 A,
respectively. The crystal structures reveal that the xenobiotic
substrate-binding site (H-site) is located at a position similar to that
observed in class mu GST 1-1 from rat liver (rGSTM1-1). In rGSTM1-1, the H-site
is a hydrophobic cavity defined by the side chains of Y6, W7, V9, L12, I111,
Y115, F208, and S209. In hGSTP1-1, the cavity is approximately half hydrophobic
and half hydrophilic and is defined by the side chains of Y7, F8, V10, R13,
V104, Y108, N204, and G205 and five water molecules. A hydrogen bond network
connects the five water molecules and the side chains of R13 and N204. V104 is
positioned such that the introduction of a methyl group (the result of the V104I
mutation) disturbs the H-site water structure and alters the substrate-binding
properties of the isozyme. The hydroxyl group of Y7 forms a hydrogen bond (3.2
A) with the sulfur atom of the product. There is a short hydrogen bond (2.5 A)
between Y108 (OH) and (9R, 10R)-GSPhen (O5), indicating the hydroxyl group of
Y108 as an electrophilic participant in the addition of glutathione to epoxides.
An N-(2-hydroxethyl)piperazine-N'-2-ethanesulfonic acid (HEPES) molecule is
found in the cavity between beta2 and alphaI. The location and properties of
this HEPES-binding site fit a possible non-substrate-binding site that is
involved in noncompetitive inhibition of the enzyme.
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Secondary reference #1
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Title
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Structure and function of the xenobiotic substrate binding site of a glutathione s-Transferase as revealed by x-Ray crystallographic analysis of product complexes with the diastereomers of 9-(S-Glutathionyl)-10-Hydroxy-9,10-Dihydrophenanthrene.
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Authors
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X.Ji,
W.W.Johnson,
M.A.Sesay,
L.Dickert,
S.M.Prasad,
H.L.Ammon,
R.N.Armstrong,
G.L.Gilliland.
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Ref.
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Biochemistry, 1994,
33,
1043-1052.
[DOI no: ]
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PubMed id
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Secondary reference #2
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Title
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Naturally occurring human glutathione s-Transferase gstp1-1 isoforms with isoleucine and valine in position 104 differ in enzymic properties.
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Authors
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P.Zimniak,
B.Nanduri,
S.Pikuła,
J.Bandorowicz-Pikuła,
S.S.Singhal,
S.K.Srivastava,
S.Awasthi,
Y.C.Awasthi.
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Ref.
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Eur J Biochem, 1994,
224,
893-899.
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PubMed id
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Secondary reference #3
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Title
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Three-Dimensional structure of class pi glutathione s-Transferase from human placenta in complex with s-Hexylglutathione at 2.8 a resolution.
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Authors
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P.Reinemer,
H.W.Dirr,
R.Ladenstein,
R.Huber,
M.Lo bello,
G.Federici,
M.W.Parker.
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Ref.
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J Mol Biol, 1992,
227,
214-226.
[DOI no: ]
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PubMed id
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Figure 8.
Figure 8. Conolly dot surface of the op region of human class x glutathione S-transferase showing both active sites
occupied by S-hexyllutathione. View is along the local dyad. Also shown is the cavity formed between the 2 subunits.
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Figure 9.
Figure 9. Model o inhibitor S-hexylglutathione and its next neighbors at the active site of human
-transferase.
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The above figures are
reproduced from the cited reference
with permission from Elsevier
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