4pgt
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CRYSTAL STRUCTURE OF HGSTP1-1[V104] COMPLEXED WITH THE GSH CONJUGATE OF (+)-ANTI-BPDE
OverviewOverview
Two variants of human class pi glutathione (GSH) S-transferase 1-1 with, either isoleucine or valine in position 104 (hGSTP1-1[I104] and, hGSTP1-1[V104]) have distinct activity toward (+)-anti-7, 8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE]. To, elucidate their structure-function relationship, we determined the crystal, structures of the two variants in complex with GSBpd, the GSH conjugate of, (+)-anti-BPDE, at 2.1 and 2.0 A resolution, respectively. The crystal, structures reveal that residue 104 in the xenobiotic substrate-binding, site (H-site) dictates the binding modes of the product molecule GSBpd, with the following three consequences. First, the distance between the, hydroxyl group of Y7 and the sulfur atom of GSBpd is 5.9 A in the, hGSTP1-1[I104].GSBpd complex versus 3.2 A in the V104 variant. Second, one, of the hydroxyl groups of GSBpd forms a direct hydrogen bond with R13 in, hGSTP1-1[V104].GSBpd; in contrast, this hydrogen bond is not observed in, the I104 complex. Third, in the hydrophilic portion of the H-site of the, I104 complex, five H-site water molecules [Ji, X., et al. (1997), Biochemistry 36, 9690-9702] are observed, whereas in the V104 complex, two, of the five have been displaced by the Bpd moiety of GSBpd. Although there, is no direct hydrogen bond between Y108 (OH) and the hydroxyl groups of, GSBpd, indirect hydrogen bonds mediated by water molecules are observed in, both complexes, supporting the previously suggested role of the hydroxyl, group of Y108 as an electrophilic participant in the addition of GSH to, epoxides.
About this StructureAbout this Structure
4PGT is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Glutathione transferase, with EC number 2.5.1.18 Full crystallographic information is available from OCA.
ReferenceReference
Structure and function of residue 104 and water molecules in the xenobiotic substrate-binding site in human glutathione S-transferase P1-1., Ji X, Blaszczyk J, Xiao B, O'Donnell R, Hu X, Herzog C, Singh SV, Zimniak P, Biochemistry. 1999 Aug 10;38(32):10231-8. PMID:10441116 [[Category: hgstp1-1[v104]]]
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