1oe7
From Proteopedia
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| , resolution 1.80Å | |||||||
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| Activity: | Glutathione transferase, with EC number 2.5.1.18 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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
Page seeded by OCA on Sun Mar 30 22:43:59 2008
