PDBsum entry 1pgt

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Transferase PDB id
Protein chain
210 a.a. *
GTX ×2
EPE ×2
Waters ×326
* Residue conservation analysis

References listed in PDB file
Key reference
Title 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.
Authors X.Ji, M.Tordova, R.O'Donnell, J.F.Parsons, J.B.Hayden, G.L.Gilliland, P.Zimniak.
Ref. Biochemistry, 1997, 36, 9690-9702. [DOI no: 10.1021/bi970805s]
PubMed id 9245401
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.
Secondary reference #1
Title 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.
Authors X.Ji, W.W.Johnson, M.A.Sesay, L.Dickert, S.M.Prasad, H.L.Ammon, R.N.Armstrong, G.L.Gilliland.
Ref. Biochemistry, 1994, 33, 1043-1052. [DOI no: 10.1021/bi00171a002]
PubMed id 8110735
Full text Abstract
Secondary reference #2
Title Naturally occurring human glutathione s-Transferase gstp1-1 isoforms with isoleucine and valine in position 104 differ in enzymic properties.
Authors P.Zimniak, B.Nanduri, S.Pikuła, J.Bandorowicz-Pikuła, S.S.Singhal, S.K.Srivastava, S.Awasthi, Y.C.Awasthi.
Ref. Eur J Biochem, 1994, 224, 893-899.
PubMed id 7925413
Secondary reference #3
Title Three-Dimensional structure of class pi glutathione s-Transferase from human placenta in complex with s-Hexylglutathione at 2.8 a resolution.
Authors P.Reinemer, H.W.Dirr, R.Ladenstein, R.Huber, M.Lo bello, G.Federici, M.W.Parker.
Ref. J Mol Biol, 1992, 227, 214-226. [DOI no: 10.1016/0022-2836(92)90692-D]
PubMed id 1522586
Full text Abstract
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.
Figure 9.
Figure 9. Model o inhibitor S-hexylglutathione and its next neighbors at the active site of human -transferase.
The above figures are reproduced from the cited reference with permission from Elsevier
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