1PGT

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

Summary for 1PGT

• Entry DOI: 10.2210/pdb1pgt/pdb
• Descriptor: GLUTATHIONE S-TRANSFERASE, S-HEXYLGLUTATHIONE, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (4 entities in total)
• Functional Keywords: transferase, pi class, hgstp1-1[v104], detoxification
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 47989.08

Authors

Ji, X. (deposition date: 1997-02-17, release date: 1997-09-04, Last modification date: 2023-08-30)

Primary citation

Ji, X.,Tordova, M.,O'Donnell, R.,Parsons, J.F.,Hayden, J.B.,Gilliland, G.L.,Zimniak, P.
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.
Biochemistry, 36:9690-9702, 1997

PubMed Abstract: 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.

PubMed: 9245401
DOI: 10.1021/bi970805s

Experimental method

X-RAY DIFFRACTION (1.8 Å)