Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
J Steroid Biochem Mol Biol. 2023 Sep;232:106353. doi: 10.1016/j.jsbmb.2023.106353. Epub 2023 Jun 17.
A central part of human sulfation pathways is the spatially and temporally controlled desulfation of biologically highly potent steroid hormones. The responsible enzyme - steroid sulfatase (STS) - is highly expressed in placenta and peripheral tissues, such as fat, colon, and the brain. The shape of this enzyme and its mechanism are probably unique in biochemistry. STS was believed to be a transmembrane protein, spanning the Golgi double-membrane by stem region formed by two extended internal alpha-helices. New crystallographic data however challenge this view. STS now is portraited as a trimeric membrane-associated complex. We discuss the impact of these results on STS function and sulfation pathways in general and we hypothesis that this new STS structural understanding suggests product inhibition to be a regulator of STS enzymatic activity.
人类磺化途径的一个核心部分是具有生物活性的甾体激素的时空控制去磺化。负责这一过程的酶——甾体硫酸酯酶（STS）——在胎盘和外周组织（如脂肪、结肠和大脑）中高度表达。这种酶的形状及其机制在生物化学中可能是独一无二的。STS 曾被认为是一种跨膜蛋白，通过由两个延伸的内部α-螺旋形成的茎区跨越高尔基体的双层膜。然而，新的晶体学数据挑战了这一观点。现在 STS 被描绘为一个三聚体膜相关复合物。我们讨论了这些结果对 STS 功能和一般磺化途径的影响，并假设对 STS 结构的这种新认识表明产物抑制是 STS 酶活性的调节剂。
