The primary function of human sulfotransferase 2B1b (SULT2B1b) is to sulfonate cholesterol and closely related sterols. SULT2B1b sterols perform a number of essential cellular functions. Many are signaling molecules whose activities are redefined by sulfonation—allosteric properties are switched “on” or “off,” agonists are transformed into antagonists, and vice versa. Sterol sulfonation is tightly coupled to cholesterol homeostasis, and sulfonation imbalances are causally linked to cholesterol-related diseases including certain cancers, Alzheimer disease, and recessive X-linked ichthyosis—an orphan skin disease. Numerous studies link SULT2B1b activity to disease-relevant molecular processes. Here, these multifaceted processes are integrated into metabolic maps that highlight their interdependence and how their actions are regulated and coordinated by SULT2B1b oxysterol sulfonation. The maps help explain why SULT2B1b inhibition arrests the growth of certain cancers and make the novel prediction that SULT2B1b inhibition will suppress production of amyloid β (Aβ) plaques and tau fibrils while simultaneously stimulating Aβ plaque phagocytosis. SULT2B1b harbors a sterol-selective allosteric site whose structure is discussed as a template for creating inhibitors to regulate SULT2B1b and its associated biology.

中文翻译：

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磺基转移酶 2B1b、甾醇磺化和疾病

人磺基转移酶 2B1b (SULT2B1b) 的主要功能是磺化胆固醇和密切相关的甾醇。SULT2B1b 甾醇执行许多重要的细胞功能。许多信号分子的活性被磺化重新定义——变构特性“打开”或“关闭”，激动剂转化为拮抗剂，反之亦然。甾醇磺化与胆固醇稳态密切相关，磺化失衡与胆固醇相关疾病有因果关系，包括某些癌症、阿尔茨海默病和隐性 X 连锁鱼鳞病（一种孤儿皮肤病）。许多研究将 SULT2B1b 活性与疾病相关的分子过程联系起来。这里，这些多方面的过程被整合到代谢图谱中，突出了它们的相互依赖性以及它们的作用如何受 SULT2B1b 氧固醇磺化作用的调节和协调。这些图有助于解释为什么 SULT2B1b 抑制会阻止某些癌症的生长，并做出新的预测，即 SULT2B1b 抑制会抑制淀粉样蛋白的产生β (A β ) 斑块和 tau 原纤维同时刺激 A β斑块吞噬作用。SULT2B1b 包含一个甾醇选择性变构位点，其结构被讨论为创建抑制剂以调节 SULT2B1b 及其相关生物学的模板。