4pgt

CRYSTAL STRUCTURE OF HGSTP1-1[V104] COMPLEXED WITH THE GSH CONJUGATE OF (+)-ANTI-BPDECRYSTAL STRUCTURE OF HGSTP1-1[V104] COMPLEXED WITH THE GSH CONJUGATE OF (+)-ANTI-BPDE

Structural highlights 4pgt is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , NonStd Res: Related: 1pgt, 2pgt, 3pgt Gene: GTP_HUMAN (Homo sapiens) Activity: Glutathione transferase, with EC number 2.5.1.18 Resources: FirstGlance, OCA, RCSB, PDBsum Function [GSTP1_HUMAN] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glutathione S-transferase

spinqualitylabelsall models 4pgt, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image