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- W69340533 abstract "Human hydroxysteroid sulfotransferase (hSULT2A1) catalyzes the sulfation of a broad range of endogenous (e.g., hormones, neurotransmitters, bile acids) as well as xenobiotic (e.g, drugs, environmental pollutants) compounds. Alteration in the catalytic activity of hSULT2A1 can lead to outcomes like endocrine disruptions or aberrant drug metabolism and xenobiotic toxicity. Oxidative and electrophilic stresses are known to cause physiological damage and be implicated as possible underlying pathologic mechanisms of a wide range of diseases. To examine the oxidative as well as electrophilic regulation of hSULT2A1, model oxidants (glutathione disulfide (GSSG), 5,5’-dithiobis(2nitrobenzoic acid) (DTNB), diamide, tert-butyl hydroperoxide (TBHP)) and electrophiles such as quinone metabolites of polychlorinated biphenyls (PCB-quinones) and phenyl-pbenzoquinone (PBQ) were chosen for this study. Mechanistic studies correlating the enzyme structural modifications with alteration in the catalytic properties were performed to elucidate the catalytic regulative mechanism of an individual oxidant or electrophile. Thiol oxidants including GSSG, DTNB, and diamide showed catalytic regulation of hSULT2A1. Changes in protein intrinsic fluorescence indicated conformational alterations in hSULT2A1 following the reaction with diamide. Binding properties of hSULT2A1 for its substrates were also altered after reaction with these thiol oxidants, which could be one major reason for the kinetic alteration due to oxidative modification. Formation of mixed disulfides with cysteines in hSULT2A1 was also identified as a result of reaction with GSSG and DTNB. TBHP was chosen as a model for lipid peroxides, and reaction with this hydroperoxide decreased the catalytic function of hSULT2A1. The dissociation constant for binding of dehydroepiandrosterone (DHEA) was significantly altered with TBHPpretreatment, but this did not affect the binding of 3’,5’-adenosine diphosphate (PAP) to the enzyme. Structural analysis identified cysteine sulfonic acids and methionine sulfoxide" @default.
- W69340533 created "2016-06-24" @default.
- W69340533 creator A5037666923 @default.
- W69340533 date "2018-11-29" @default.
- W69340533 modified "2023-10-11" @default.
- W69340533 title "Oxidative and electrophilic structural modification and catalytic regulation of human hydroxysteroid sulfotransferase 2a1 (hsult2a1)" @default.
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