1OE7

28kDa glutathione S-transferase from Schistosoma haematobium

Summary for 1OE7

• Entry DOI: 10.2210/pdb1oe7/pdb
• Related: 1OE8
• Descriptor: GLUTATHIONE S-TRANSFERASE, GLUTATHIONE (3 entities in total)
• Functional Keywords: transferase, schistosomiasis, detoxifying enzyme, prostaglandin d2 synthase, vaccine candidate
• Biological source: SCHISTOSOMA HAEMATOBIUM (BLOOD FLUKE)
• Total number of polymer chains: 2
• Total formula weight: 48488.14

Authors

Johnson, K.A.,Angelucci, F.,Tsernoglou, D. (deposition date: 2003-03-19, release date: 2003-07-25, Last modification date: 2023-12-13)

Primary citation

Johnson, K.A.,Angelucci, F.,Bellelli, A.,Herve, M.,Fontaine, J.,Tsernoglou, D.,Capron, A.,Trottein, F.,Brunori, M.
Crystal Structure of the 28 kDa Glutathione S-Transferase from Schistosoma Haematobium
Biochemistry, 42:10084-, 2003

PubMed Abstract: Schistomiasis is a debilitating parasitic disease which affects 200 million people, causing life-threatening complications in 10% of the patients. This paper reports the crystal structure of the Schistosoma haematobium 28 kDa glutathione S-transferase, a multifunctional enzyme involved in host-parasite interactions and presently considered as a promising vaccine candidate against schistosomiasis. The structures of the GSH-free enzyme, as well as the partially (approximately 40%) and almost fully (approximately 80%) GSH-saturated enzyme, exhibit a unique feature, absent in previous GST structures, concerning the crucial and invariant Tyr10 side chain which occupies two alternative positions. The canonical conformer, which allows an H-bond to be formed between the side chain hydroxyl group and the activated thiolate of GSH, is somewhat less than 50% occupied. The new conformer, with the phenoxyl ring on the opposite side of the mobile loop connecting strand 1 and helix 1, is stabilized by a polar interaction with the guanidinium group of the conserved Arg21 side chain. The presence of two conformers of Tyr10 may provide a clue about clarifying the multiple catalytic functions of Sh28GST and might prove to be relevant for the design of specific antischistosomal drugs. The K(d) for GSH binding was determined by equilibrium fluorescence titrations to be approximately 3 microM and by stopped-flow rapid mixing experiments to be approximately 9 microM. The relatively tight binding of GSH by Sh28GST explains the residually bound GSH in the crystal and supports a possible role of GSH as a tightly bound cofactor involved in the catalytic mechanism for prostaglandin D(2) synthase activity.

PubMed: 12939136
DOI: 10.1021/BI034449R

Experimental method

X-RAY DIFFRACTION (1.8 Å)