1k0c
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Ure2p in complex with S-p-nitrobenzylglutathione
OverviewOverview
The [URE3] phenotype in yeast Saccharomyces cerevisiae is due to an, altered prion form of Ure2p, a protein involved in nitrogen catabolism. To, understand possible conformational changes at the origin of prion, propagation, we previously solved the crystal structure of the Ure2p, functional region [Bousset et al. (2001) Structure 9, 39-46]. We showed, the protein to have a fold similar to that of the beta class of, glutathione S-transferases (GSTs). Here we report crystal structures of, the Ure2p functional region (extending from residues 95-354) in complex, with glutathione (GSH), the substrate of all GSTs, and two widely used GST, inhibitors, namely, S-hexylglutathione and S-p-nitrobenzylglutathione. In, a manner similar to what is observed in many GSTs, ligand binding is not, accompanied by a significant change in the conformation of the protein. We, identify one GSH and one hydrophobic electrophile binding site per monomer, as observed in all other GSTs. The sulfur group of GSH, that conjugates, electrophiles, is located near the amide group of Asn124, allowing a, hydrogen bond to be formed. Biochemical data indicate that GSH binds to, Ure2p with high affinity. Its binding affects Ure2p oligomerization but, has no effect on the assembly of the protein into amyloid fibrils. Despite, results indicating that Ure2p lacks GST activity, we propose that Ure2p is, a member of the GST superfamily that may describe a novel GST class. Our, data bring new insights into the function of the Ure2p active region.
About this StructureAbout this Structure
1K0C is a Single protein structure of sequence from Saccharomyces cerevisiae with GTB and GTT as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of the yeast prion Ure2p functional region in complex with glutathione and related compounds., Bousset L, Belrhali H, Melki R, Morera S, Biochemistry. 2001 Nov 13;40(45):13564-73. PMID:11695904
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