ABSTRACT

Diol Epoxides...............................................................................................107 6.3.1 Specificity of Rat GSTs ...................................................................107 6.3.2 Specificity of Murine GSTs.............................................................107 6.3.3 Structural Basis for Catalytic Differences between

mGSTA1-1 and mGSTA2-2 toward PAH Diol Epoxides ...............109 6.4 Crystal Structures of mGSTA1-1 and mGSTA2-2 in Complex

with GSH Conjugate of (+)-

anti

-BPDE ......................................................110 6.4.1 Active Center and Binding of GSH Conjugate of

(+)-

anti

-BPDE (GSBpd) in mGSTA1-1 ..........................................110 6.4.2 Xenobiotic-Induced Conformational Changes in mGSTA1-1 ........112 6.4.3 H-Site Comparison of mGSTA1-1 with mGSTA4-4 ......................112 6.4.4 Role of Arg-216 in mGSTA1-1-Catalyzed GSH Conjugation

of (+)-

anti

-BPDE .............................................................................113 6.4.5 GSBpd Binding in the Active Center of mGSTA2-2......................113

6.5 Specificity of Human GSTs toward PAH Diol Epoxides ...........................115 6.5.1 Kinetic Analysis of Human GSTs toward Diol Epoxides...............115 6.5.2 Structural Basis for Catalytic Differences between hGSTA1-1