6533b853fe1ef96bd12ac11f
RESEARCH PRODUCT
Detoxication of carcinogenic fjord-region diol epoxides of polycyclic aromatic hydrocarbons by glutathione transferase P1-1 variants and glutathione.
Bengt JernströmKathrin SundbergBengt MannervikAlbrecht Seidelsubject
StereochemistryCarcinogenesisMutantBiophysicsPolycyclic aromatic hydrocarbonurologic and male genital diseasesBiochemistryCatalysischemistry.chemical_compoundStructure-Activity RelationshipStructural BiologyGeneticspolycyclic compoundsStructure–activity relationshipHumansGlutathione conjugationPolycyclic Aromatic HydrocarbonsMolecular BiologyGeneneoplasmsCarcinogenGlutathione Transferasechemistry.chemical_classificationbiologyMolecular StructureChemistryActive siteGenetic VariationBiological activityCell BiologyGlutathioneGlutathioneFjord regionPolycyclic aromatic hydrocarbonKineticsBiochemistryDiol epoxideHuman glutathione transferase P1-1Inactivation Metabolicbiology.proteinCarcinogensdescription
AbstractEpidemiological studies suggest that individuals differing in the expression of allelic variants of the human glutathione transferase (GST) Pi gene differ in susceptibility to chemical carcinogens such as polycyclic aromatic hydrocarbons (PAH). This study reports the catalytic efficiencies (kcat/Km) of two naturally occurring variants, GSTP1-1/I-105 and GSTP1-1/V-105, towards a series of fjord-region diol epoxides representing potent biologically active PAH metabolites, and two GSTP1-1 mutants with Ala105 and Trp105 in the active site. The results indicate that individuals who are homozygous for the allele encoding GSTP1-1/V-105 might be more susceptible to PAH carcinogenesis due to other reasons than a reduced capacity for detoxifying diol epoxides.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 1998-11-06 | FEBS letters |