1pgt

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spinqualitylabelsall models 1pgt, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CRYSTAL STRUCTURE OF HUMAN GLUTATHIONE S-TRANSFERASE P1-1[V104] COMPLEXED WITH S-HEXYLGLUTATHIONE

Overview

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.

About this Structure

1PGT is a Single protein structure of sequence from Homo sapiens with GTX and EPE as ligands. Active as Glutathione transferase, with EC number 2.5.1.18 Full crystallographic information is available from OCA.

Reference

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., Ji X, Tordova M, O'Donnell R, Parsons JF, Hayden JB, Gilliland GL, Zimniak P, Biochemistry. 1997 Aug 12;36(32):9690-702. PMID:9245401[[Category: hgstp1-1[v104]]]

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