Rozhin J, Huo A, Zemlicka J, Brooks S C
J Biol Chem. 1977 Oct 25;252(20):7214-20.
The inhibition of bovine adrenal estrogen sulfotransferase has been studied utilizing representative androgens and estrogens with structural changes in rings A, B, and D. These investigations have shown oxygen functions in positions 3, 16, or 17 to be required for the binding of estrogens or androgens to the enzyme. 5alpha-Androstanes (all transfused rings) are weak noncompetitive inhibitors and bind more tightly than the 5beta isomers (cis-fused A and B rings). The competitive inhibition observed with the estrogens does not require a free 3-phenolic hydroxyl, however, groups larger than 3-methoxy limit binding. While the product, estrone sulfate, is not inhibitory, phosphate esters on positions 3- or 17beta or a sulfate moiety on the 17beta-hydroxyl group of estrogens slightly inhibit the enzyme. The stacking of adenine (in adenosine 3'-phosphate-5'-phosphosulfate) with the A ring of estrogens is postulated for the enzyme-bound transition state. This structure, which facilitates the hydrogen bonding between the 6-amino group of adenine and the 4-nitro, 4-bromo, or 6-keto substituents on estrogens, readily explains the unusual substrate and inhibitory properties of these compounds. Certain of these estrogen derivatives, which possess little or no hormonal activity, are efficient inhibitors of estrogen sulotransferase.
利用具有A、B和D环结构变化的代表性雄激素和雌激素，对牛肾上腺雌激素硫酸转移酶的抑制作用进行了研究。这些研究表明，雌激素或雄激素与该酶结合需要在3、16或17位上具有氧官能团。5α-雄甾烷（所有环均为反式稠合）是弱非竞争性抑制剂，其结合比5β异构体（A和B环为顺式稠合）更紧密。然而，雌激素观察到的竞争性抑制作用并不需要游离的3-酚羟基，但是，大于3-甲氧基的基团会限制结合。虽然产物硫酸雌酮没有抑制作用，但雌激素3-位或17β-位上的磷酸酯或17β-羟基上的硫酸基团会轻微抑制该酶。推测在酶结合的过渡态中，腺嘌呤（在3'-磷酸-5'-磷酸硫酸腺苷中）与雌激素的A环发生堆积。这种结构促进了腺嘌呤的6-氨基与雌激素上的4-硝基、4-溴或6-酮取代基之间的氢键形成，这很容易解释这些化合物不同寻常的底物和抑制特性。这些雌激素衍生物中有些几乎没有或完全没有激素活性，但却是雌激素硫酸转移酶的有效抑制剂。
