1oe7

From Proteopedia

Revision as of 14:46, 5 November 2007

28KDA GLUTATHIONE S-TRANSFERASE FROM SCHISTOSOMA HAEMATOBIUM

Overview

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.

About this Structure

1OE7 is a Single protein structure of sequence from Schistosoma haematobium with GSH as ligand. Active as Glutathione transferase, with EC number 2.5.1.18 Structure known Active Site: AC1. Full crystallographic information is available from OCA.

Reference

Crystal structure of the 28 kDa glutathione S-transferase from Schistosoma haematobium., Johnson KA, Angelucci F, Bellelli A, Herve M, Fontaine J, Tsernoglou D, Capron A, Trottein F, Brunori M, Biochemistry. 2003 Sep 2;42(34):10084-94. PMID:12939136

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